Prosthesis and deployment catheter for treating vascular bifurcations

ABSTRACT

A stepped balloon catheter prosthesis deployment system is disclosed for placement of a prosthesis across an Os opening from a main body lumen to a branch body lumen. The prosthesis comprises a radially expansible support at one end, a circumferentially extending link at the other end and at least one frond extending axially therebetween. The prosthesis is configured to be deployed from a stepped diameter balloon with the support in the branch body lumen, with the circumferentially extending link in the main lumen and the frond extendable across the Os.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.10/584,968 filed Jun. 30, 2006, which is a U.S. National Phase under 35U.S.C. § 371 of International Application PCT/US2005/036987, filed Oct.13, 2005 and published in English on Apr. 27, 2006 and is a Continuationof U.S. patent application Ser. No. 11/249,138, filed on Oct. 12, 2005,which is a Continuation-In-Part of U.S. patent application Ser. No.11/190,514 filed on Jul. 27, 2005 which is a Continuation-in-Part ofU.S. patent application Ser. No. 11/076,448 filed on Mar. 9, 2005, whichis a Continuation-in-Part of co-pending U.S. patent application Ser. No.10/807,643 filed on Mar. 23, 2004, which claims the benefit of priorityof U.S. Provisional Application No. 60/463,075, filed on Apr. 14, 2003,the full disclosures of which are incorporated in their entiretiesherein by reference. U.S. patent application Ser. No. 11/249,138 also isa Continuation-In-Part of U.S. patent application Ser. No. 10/965,230,filed on Oct. 13, 2004, and the full disclosure of which is incorporatedby reference in its entirety herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Embodiments of the present invention relate generally to medical devicesand methods. More particularly, embodiments of the present inventionrelate to the structure and deployment of a prosthesis having a stent orother support structure and at least one, and in some implementations atleast two fronds for deployment at a branching point in the vasculatureor elsewhere.

Maintaining the patency of body lumens is of interest in the treatmentof a variety of diseases. Of particular interest to the presentinvention are the transluminal approaches to the treatment of bodylumens. More particularly, the percutaneous treatment of atheroscleroticdisease involving the coronary and peripheral arterial systems.Currently, percutaneous coronary interventions (PCI) often involve acombination of balloon dilation of a coronary stenosis (i.e. a narrowingor blockage of the artery) followed by the placement of an endovascularprosthesis commonly referred to as a stent.

A major limitation of PCI/stent procedures is restenosis, i.e., there-narrowing of a blockage after successful intervention typicallyoccurring in the initial three to six months post treatment. The recentintroduction of drug eluting stents (DES) has dramatically reduced theincidence of restenosis in coronary vascular applications and offerspromise in peripheral stents, venous grafts, arterial and prostheticgrafts, as well as A-V fistulae. In addition to vascular applications,stents are being employed in treatment of other body lumens includingthe gastrointestinal systems (esophagus, large and small intestines,biliary system and pancreatic ducts) and the genital-urinary system(ureter, urethra, fallopian tubes, vas deferens).

Treatment of lesions in and around branch points generally referred toas bifurcated vessels, is a developing area for stent applications,particularly, since at least about 5%-10% of all coronary lesionsinvolve bifurcations. However, while quite successful in treatingarterial blockages and other conditions, current stent designs arechallenged when used at a bifurcation in the blood vessel or other bodylumen. Presently, many different strategies are employed to treatbifurcation lesions with currently available stents all of which havemajor limitations.

One common approach is to place a conventional stent in the main orlarger body lumen over the origin of the side branch. After removal ofthe stent delivery balloon, a second wire is introduced through a cellin the wall of the deployed stent and into the side branch. A balloon isthen introduced into the side branch and inflated to enlarge theside-cell of the main vessel stent. This approach can work well when theside branch is relatively free of disease, although it is associatedwith increased rates of abrupt closure due to plaque shift anddissection as well as increased rates of late restenosis.

Another commonly employed strategy is the ‘kissing balloon’ technique inwhich separate balloons are positioned in the main and side branchvessels and simultaneously inflated to deliver separate stentssimultaneously. This technique is thought to prevent plaque shift.

Other two-stent approaches including Culotte, T-Stent and Crush Stenttechniques have been employed as well. When employing a T-Stentapproach, the operator deploys a stent in the side branch followed byplacement of a main vessel stent. This approach is limited by anatomicvariation (angle between main and side branch) and inaccuracy in stentpositioning, which together can cause inadequate stent coverage of theside branch origin commonly referred to as the ostium or Os. Morerecently, the Crush approach has been introduced in which theside-vessel stent is deployed across the Os with portions in both themain and side branch vessels. The main vessel stent is then deliveredacross the origin of the side branch and deployed, which results incrushing a portion of the side branch stent between the main vesselstent and the wall of the main vessel. Following main-vessel stentdeployment, it is difficult and frequently not possible to re-enter theside branch after crush stenting. Unproven long-term results coupledwith concern regarding the inability to re-enter the side branch,malaposition of the stents against the arterial wall and the impact ofthree layers of stent (which may be drug eluting) opposed against themain vessel wall has limited the adoption of this approach.

These limitations have led to the development of stents specificallydesigned to treat bifurcated lesions. One approach employs a stentdesign with a side opening for the branch vessel which is mounted on aspecialized balloon delivery system. The specialized balloon deliverysystem accommodates wires for both the main and side branch vessels. Thesystem is tracked over both wires which provides a means to axially andradially align the stent/stent delivery system. The specialized mainvessel stent is then deployed and the stent delivery system removedwhile maintaining wire position in both the main and side branchvessels. The side branch is then addressed using the kissing balloontechnique or by delivering an additional stent to the side branch.Though this approach has many theoretical advantages, it is limited bydifficulties in tracking the delivery system over two wires (See, e.g.,U.S. Pat. Nos. 6,325,826 and 6,210,429 to Vardi et al.).

Notwithstanding the foregoing efforts, there remains a need for improveddevices as well as systems and methods for delivering devices, to treatbody lumens at or near the location of an Os between a main body lumenand a side branch lumen, typically in the vasculature, and moreparticularly in the arterial vasculature. It would be further desirableif such systems and methods could achieve both sufficient radial supportas well as adequate surface area coverage in the region of the Os andthat the prostheses in the side branches be well-anchored at or near theOs.

2. Description of the Related Art

Stent structures intended for treating bifurcated lesions are describedin U.S. Pat. Nos. 6,599,316; 6,596,020; 6,325,826; and 6,210,429. Otherstents and prostheses of interest are described in the following U.S.Pat. Nos. 4,994,071; 5,102,417; 5,342,387; 5,507,769; 5,575,817;5,607,444; 5,609,627; 5,613,980; 5,669,924; 5,669,932; 5,720,735;5,741,325; 5,749,825; 5,755,734; 5,755,735; 5,824,052; 5,827,320;5,855,598; 5,860,998; 5,868,777; 5,893,887; 5,897,588; 5,906,640;5,906,641; 5,967,971; 6,017,363; 6,033,434; 6,033,435; 6,048,361;6,051,020; 6,056,775; 6,090,133; 6,096,073; 6,099,497; 6,099,560;6,129,738; 6,165,195; 6,221,080; 6,221,098; 6,254,593; 6,258,116;6,264,682; 6,346,089; 6,361,544; 6,383,213; 6,387,120; 6,409,750;6,428,567; 6,436,104; 6,436,134; 6,440,165; 6,482,211; 6,508,836;6,579,312; and 6,582,394.

SUMMARY OF THE INVENTION

There is provided in accordance with one aspect of the presentinvention, a prosthesis for placement at an ostium or Os opening from amain body lumen to a branch body lumen. The prosthesis comprises aradially expansible branch vessel support, configured to be deployed inat least a portion of the branch body lumen. At least one, and in someimplementations a plurality of fronds extend axially from the support. Aradially expansible connector, spaced axially apart from the branchvessel support is provided for connecting at least two points on thefrond, and optionally at least two or all of the fronds in a multi frondimplementation of the invention.

In accordance with a further aspect of the present invention, there isprovided a method for treating a bifurcation between a main lumen and abranch lumen. The method comprises the steps of providing a radiallyexpandable scaffold, having a proximal end, a distal end, a supportstructure on the distal end, a circumferential link on the proximal endand at least two fronds extending axially between the support structureand the circumferential link. The scaffold is transluminally navigatedto a treatment site, and deployed at the site such that the support isin the branch lumen and the circumferential link is in the main lumen.

The method may additionally comprise a step of positioning an inflatableballoon in the main lumen, and deforming the circumferential link suchthat it conforms to at least a portion of the wall of the main lumen.The method may additionally comprise the step of deploying a stent inthe main lumen, to trap fronds between the main vessel stent and theadjacent vessel wall.

In accordance with a further aspect of the present invention, there isprovided a prosthesis for placement at an opening from a main body lumento a branch body lumen. The prosthesis comprises a radially expansiblesupport, the support configured to be deployed in at least a portion ofthe branch body lumen. A plurality of fronds extend axially from thesupport, and at least one circumferential link connects at least a firstand a second frond, the circumferential link spaced axially apart fromthe support. Preferably, the circumferential link connects each of theplurality of fronds. At least a portion of the prosthesis may beprovided with a drug coating. The drug coating may be a drug elutingcoating, and may be configured to exhibit at least one of a controlleddrug release rate, a constant release rate, bi-modal drug release rate,or a controlled concentration of drug proximate a target vessel wall.

There is provided in accordance with one aspect of the presentinvention, a prosthesis and deployment system assembly. The assemblycomprises an elongate flexible catheter body, having a balloon thereon.The balloon has an inflated profile with a first section having a firstdiameter, a second section having a second diameter, and a balloontransition in-between the first and second sections. A prosthesis iscarried by the balloon. The prosthesis has a wall, having a first wallpattern adjacent the first section of the balloon, and a second wallpattern adjacent the balloon transition. In one embodiment, theprosthesis has a third wall pattern adjacent the second section of theballoon.

There is provided in accordance with another aspect of the presentinvention, a prosthesis and deployment catheter system for treating anopening from a main body lumen to a branch body lumen. The prosthesiscomprises a radially expansible support, the support configured to bedeployed in at least a portion of the branch body lumen. A plurality offronds extends axially from an end of the support, and are configured tobe positioned across the Os and into the main body lumen. At least onecircumferential link connects at least a first and a second frond, thecircumferential link spaced axially apart from the support.

The prosthesis is mounted on a balloon catheter, such that the radiallyexpansible support is carried by a first portion of a balloon that isinflatable to a first diameter, and the circumferential link is carriedby a second portion of a balloon that is inflatable to a seconddiameter, that is larger than the first diameter.

The circumferential link may connect each of the plurality of fronds.Preferably, the plurality of fronds includes at least three fronds. Eachfrond may comprise a resilient metal.

At least a portion of the resiliently expansible support may comprise adrug coating, and at least a portion of the fronds and thecircumferential link are without a drug coating. The drug coating may bea drug eluting coating, and may be configured to produce at least one ofa controlled drug delivery rate, a constant drug delivery rate, bimodaldrug release rate, or a controlled concentration of drug proximate atarget vessel wall. The drug may be configured to reduce an incidence oramount of restenosis.

In accordance with further aspect of the present invention, there isprovided a method of treating a patient. The method comprises the stepsof providing a catheter having a balloon with at least a first sectionhaving a relatively small inflated diameter and a second section havinga relatively larger inflated diameter. The balloon is positioned acrossthe opening of a branch vessel from a main vessel. The balloon isthereafter inflated such that the first section is inflated at leastpartially within the branch vessel and the second section is inflated atleast partially within the main vessel.

The providing a catheter step preferably comprises providing a catheterhaving an implantable prosthesis mounted on the balloon. The prosthesismay have a first zone carried by a first section of the balloon and asecond zone carried by a second section of the balloon. The prosthesismay additionally have a transition zone positioned between the firstzone and the second zone.

In accordance with a further aspect of the present invention, there isprovided a method for treating a bifurcation between a main lumen and abranch lumen. The method comprises the steps of providing a radiallyexpandable prosthesis, having a proximal end, a distal end, a supportstructure on the distal end, a circumferential link on the proximal end,and at least two fronds extending axially between the support structureand the circumferential link. The prosthesis is translumenally navigatedto the treatment site. The prosthesis is deployed at the site such thatthe support is expanded in the branch lumen by a first diameter sectionof a first deployment balloon, and the circumferential link is expandedin the main lumen by a second diameter section of the deploymentballoon.

The method may additionally comprise the step of positioning a secondinflatable balloon in the main lumen, and deforming at least one frondsuch that it conforms to at least a portion of the wall of the mainlumen. The method may comprise the additional step of deploying a stentin the main lumen.

Further features and advantages of the present invention will becomeapparent from the detailed description of preferred embodiments whichfollows, when considered together with the attached drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a prosthesis constructed inaccordance with the principles of the present invention.

FIG. 1A is a detailed view of the fronds of the prosthesis of FIG. 1,shown with the fronds deployed in broken line.

FIG. 2 is a cross-sectional view taken along line 2-2 of FIG. 1.

FIGS. 2A-2E are lateral views showing embodiments of a stent havingfronds in a rolled out configuration. FIG. 2A shows an embodiment havingserpentine-shaped fronds, FIG. 2B shows an embodiment having filamentshaped fronds, while FIG. 2C shows an embodiment having filament shapedfronds with alternating shortened fronds. FIGS. 2D and 2E illustrate anested transition zone configuration with two different stent wallpatterns.

FIG. 2F is a lateral view as in FIG. 2D, with the added feature of acircumferential link to assist in maintaining the spacial orientation ofthe fronds.

FIGS. 3A and 3B are lateral and cross sectional views illustrating anembodiment of a stent having fronds and an underlying deployment balloonhaving a fold configuration such that the balloon folds protrude throughthe spaces between the fronds.

FIGS. 4A and 4B are lateral and cross sectional views illustrating theembodiment of FIGS. 3A and 3B with the balloon folded over to capturethe fronds.

FIGS. 5A-5C are lateral views illustrating the deployment of stentfronds using an underlying deployment balloon and a retaining cuffpositioned over the proximal portion of the balloon. FIG. 5A showspre-deployment, the balloon un-inflated; FIG. 5B shows deployment, withthe balloon inflated; and FIG. 5C post-deployment, the balloon nowdeflated.

FIGS. 6A-6B are lateral views illustrating the change in shape of thecuff during deployment of a stent with fronds. FIG. 6A shows the balloonin an unexpanded state; and FIG. 6B shows the balloon in an expandedstate, with the cuff expanded radially and shrunken axially.

FIGS. 6C-6D are lateral views illustrating an embodiment of a cuffconfigured to evert upon balloon inflation to release the fronds.

FIGS. 7A-7B are lateral views illustrating an embodiment of a tether forrestraining the stent fronds.

FIGS. 8A-8B are lateral views illustrating an embodiment of a proximallyretractable sleeve for restraining the stent fronds.

FIGS. 9A-9B, 10A-10B and 11A-11B illustrate deployment of a stent at anOs between a main blood vessel and a side branch blood vessel inaccordance with the principles of the methods of the present invention.

FIGS. 12A-12H are lateral and cross section views illustratingdeployment of a stent having filament fronds an Os between a main bloodvessel and a side branch blood vessel in accordance with the principlesof the methods of the present invention.

FIGS. 13A-13C illustrate side wall patterns for three main vessel stentsuseful in combination with the prosthesis of the present invention.

FIG. 13D is an image of a deployed main vessel stent having a side wallopening in alignment with a branch vessel.

FIGS. 14A-14E are a sequence of schematic illustrations showing thedeployment of a vascular bifurcation prosthesis with linked fronds.

FIG. 15 is a schematic profile of a stepped balloon in accordance withone aspect of the present invention.

FIG. 16 is a balloon compliance curve for one embodiment of the steppedballoon in accordance with the present invention.

FIG. 17 is a schematic representation of a stepped balloon positionedwithin a vascular bifurcation.

FIG. 18 is a schematic representation as in FIG. 17, with a differentconfiguration of stepped balloon in accordance with the presentinvention.

FIG. 19 is a first step in a deployment sequence using a stepped balloonand prosthesis in accordance with the present invention.

FIG. 20 is a second step in the deployment process disclosed inconnection with FIG. 19, in which the prosthesis is positioned acrossthe Os.

FIG. 21 is a third step in a deployment sequence, in which a prosthesishas been expanded utilizing a stepped balloon in accordance with thepresent invention.

FIG. 22 is a fourth step in a deployment sequence, in which the steppedballoon has been removed following deployment of the prosthesis acrossthe Os.

FIG. 23 is a side elevational schematic view of a distal portion of acatheter in accordance with the present invention.

FIG. 23A is a cross sectional view taken along the lines 23A-23A in FIG.23.

FIG. 23B is a cross sectional view taken along the lines 23B-23B in FIG.23.

FIG. 24 is a side elevational view as in FIG. 23, with a modifiedcatheter in accordance with the present invention.

FIG. 24A is a cross sectional view taken along the line 24A-24A of FIG.24.

FIG. 24B is a cross sectional view taken along the line 24B-24B in FIG.24.

FIG. 25 is a schematic view of a two guidewire catheter in accordancewith the present invention, in position at a vascular bifurcation.

FIG. 26 is a schematic representation as in FIG. 25, showing the secondguidewire advanced distally through the fronds.

FIG. 27 is a schematic view as in FIG. 25, with a modified two guidewirecatheter in accordance with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Embodiments of the present invention provide improved prostheses anddelivery systems for their placement within a body lumen, particularlywithin a bifurcated body lumen and more particularly at an Os openingfrom a main body lumen to a branch body lumen. The prostheses anddelivery systems will be principally useful in the vasculature, mosttypically the arterial vasculature, including the coronary, carotid andperipheral vasculature; vascular grafts including arterial, venous, andprosthetic grafts such as a bifurcated abdominal aortic aneurysm graft,and A-V fistulae. In addition to vascular applications, embodiments ofthe present invention can also be configured to be used in the treatmentof other body lumens including those in the gastrointestinal systems(e.g., esophagus, large and small intestines, biliary system andpancreatic ducts) and the genital-urinary system (e.g., ureter, urethra,fallopian tubes, vas deferens), and the like.

The prosthesis in accordance with the present invention generallycomprises three basic components: a stent or other support, at least onefrond extending from the support, and a transition zone between thesupport and the frond. These components may be integrally formed such asby molding, or by laser or other cutting from tubular stock, or may beseparately formed and secured together.

The term “fronds” as used herein will refer to any of a variety ofstructures including anchors, filaments, petals or other independentlymultiaxially deflectable elements extending from the stent or othersupport structure, to engage an adjacent main vessel stent or otherassociated structure. These fronds can expandably conform to and atleast partially circumscribe the wall of the main body vessel toselectively and stably position the prosthesis within the side branchlumen and/or optimize wall coverage in the vicinity of the ostium.Further description of exemplary frond structures and prostheses isfound in co-pending application Ser. No. 10/807,643, the full disclosureof which has previously been incorporated herein by reference. Variousembodiments of the present invention provide means for capturing orotherwise radially constraining the fronds during advancement of theprosthesis through the vasculature (or other body lumen) to a targetsite and then releasing the fronds at the desired deployment site.

The prostheses of the present invention are particularly advantageoussince they permit substantially complete coverage of the wall of thebranch body lumen up to and including the lumen ostium or Os.Additionally, the prostheses have integrated fronds which expandablyconform to and at least partially circumscribe the wall of the main bodyvessel to selectively and stably link the prosthesis to the main vesselstent. The fronds may be fully expanded to open the luminal passagethrough the main branch lumen. Such complete opening is an advantagesince it provides patency through the main branch lumen. Moreover, theopen main vessel lumen permits optional placement of a second prosthesiswithin the main branch lumen using conventional techniques.

In a first aspect of the present invention, a prosthesis comprises aradially expansible support and at least one or often two or more frondsextending axially from an end of the support. The fronds are adapted toextend around, or “expandably circumscribe” a portion of, usually atleast one-half of the circumference of the main vessel wall at or nearthe Os when the support is implanted in the branch lumen with the frondsextending into the main lumen. By “expandably circumscribe,” it is meantthat the fronds will extend into the main body lumen after initialplacement of the support within the branch body lumen. The fronds willbe adapted to then be partially or fully radially expanded, typically byexpansion of a balloon or other expandable structure therein, so thatthe fronds deform outwardly and conform to the interior surface of themain lumen.

The fronds will usually extend axially within the main vessel lumen forsome distance after complete deployment. In certain embodiments, thecontact between the fronds and the main vessel wall will usually extendboth circumferentially (typically at least one frond may cover an arcequal to one-half or more of the circumference of the main vessel) andaxially.

Deformation of the fronds to conform to at least a portion of the wallof the main body lumen provides a generally continuous coverage of theOs from the side branch lumen to the main vessel lumen. Further and/orcomplete expansion of the fronds within the main body lumen may pressthe fronds firmly against the main body lumen wall and open up thefronds so that they do not obstruct flow through the main body lumen,while maintaining patency and coverage of the side branch and os.

Usually, the prosthesis will include at least two or three frondsextending axially from the end of the support. The prosthesis couldinclude four, five, or even a greater number of fronds, but the use ofthree such fronds is presently contemplated for a coronary arteryembodiment. The fronds will have an initial length (i.e., prior toradial expansion of the prosthesis) which is at least about 1.5 timesthe width of the prosthesis prior to expansion, typically at least about2 times the width, more typically at least about 5 times the width, andoften about 7 times the width or greater. The lengths will typically beat least about 2 mm, preferably at least about 3 mm, and more preferablyat least about 6 mm. The frond length may also be considered relative tothe diameter of the corresponding main vessel. For example, a prosthesisconfigured for use in a branch vessel from a main vessel having a 3 mmlumen will preferably have a frond length of at least about 7 mm and insome embodiments at least about 9 mm.

Embodiments of the present invention incorporating only a single frondare also contemplated. The single frond may extend axially from thebranch vessel support as has been described in connection with multifrond embodiments. Alternatively, the single frond (or two or three ormore fronds) may extend in a helical or spiral pattern, such that itwraps in a helical winding about the longitudinal axis extending throughthe branch vessel support.

The fronds may have a fixed width or a width which is expandable toaccommodate the expansion of the support, and the fronds may be “hinged”at their point of connection to the support to permit freedom to adaptto the geometry of the main vessel lumen as the prosthesis is expanded.As used herein, “hinged” does not refer to a specific structure such asa conventional hinge, but rather to any combination of structures,materials and dimensions that permit multiaxial flexibility of the frondrelative to the support so that the frond can bend in any directionand/or rotate about any axis to conform to the ablumenal surface of theexpanded main vessel stent under normal use conditions. It is alsopossible that the fronds could be attached at a single point to thesupport, thus reducing the need for such expandability. The fronds maybe congruent, i.e., have identical geometries and dimensions, or mayhave different geometries and/or dimensions. In particular, in someinstances, it may be desirable to provide fronds having differentlengths and/or different widths.

In another aspect of the invention, at least one of the of fronds has aloop or filament shape and includes a first expandable strut configuredto be positioned at the Os in an expanded state and provide radialsupport to an interior portion of the main body lumen. The fronds can befabricated from flexible metal wire, molded, laser cut or otherwiseformed from tube stock in accordance with known techniques. The strutcan be configured to be substantially triangular in the expanded state.Also, at least one of the fronds may be configured to be expandablydeployed proximate a vessel wall by an expandable device such as anexpandable balloon catheter.

In another aspect of the invention, a prosthesis delivery systemcomprises a delivery catheter having an expandable member and aprosthesis carried over the expandable member. The prosthesis has aradially expandable support such as a tubular stent and at least twofronds extending axially from the support. The system also includes aretainer for capturing the fronds to prevent them from divaricating fromthe expandable member as the catheter is advanced through a patient'svasculature. “Divarication” as used herein means the separation orbranching of the fronds away from the delivery catheter. Variousembodiments of the capture means prevent divarication by constrainingand/or imparting sufficient hoop strength to the fronds to prevent themfrom branching from the expandable member during catheter advancement inthe vasculature.

In one embodiment, the capturing means comprises a portion of theexpandable member that is folded over the fronds where the foldsprotrude through axial gaps between adjacent fronds. In anotherembodiment, the capturing means comprises a cuff that extends over atleast a portion of the fronds to hold them during catheter advancement.The cuff can be positioned at the proximal end of the prosthesis and canbe removed by expansion of the expandable member to either plasticallyor elastically deform the cuff, break the cuff, or reduce the cuff inlength axially as the cuff expands circumferentially. The cuff is thenwithdrawn from the target vessel. In yet another embodiment, thecapturing means can comprise a tether which ties together the fronds.The tether can be configured to be detached from the fronds prior toexpansion of the expandable member. In alternative embodiments, thetether can be configured to break or release upon expansion of theexpandable member so as to release the fronds.

In an exemplary deployment protocol using the prosthesis deliverysystem, the delivery catheter is advanced to position the prosthesis ata target location in a body lumen. During advancement, at least aportion of the fronds are radially constrained to prevent divaricationof the fronds from the delivery catheter. When the target location isreached, the radial constraint is released and the prosthesis isdeployed within the lumen.

In various embodiments, the release of the fronds and expansion of theprosthesis can occur simultaneously or alternatively, the radialconstraint can be released prior to, during, or afterexpanding/deploying the prosthesis. In embodiments where the radialconstraint comprises balloon folds covering the fronds or a cuff ortether, the constraint can be released as the balloon is inflated. Inalternative embodiments using a cuff or tether, the cuff/tether can bewithdrawn from the fronds prior to expansion of the support.

Embodiments of the above protocol can be used to deploy the prosthesisacross the Os of a branch body lumen and trailing into the main bodylumen. In such applications, the prosthesis can be positioned so thatthe stent lies within the branch body and at least two fronds extendinto the main body lumen. The fronds are then circumferentially deformedto conform to at least a portion of the main vessel wall to define amain vessel passage through the fronds. At least two and preferably atleast three fronds extend into the main body lumen.

Radiopaque or other medical imaging visible markers can be placed on theprostheses and/or delivery balloon at desired locations. In particular,it may be desirable to provide radiopaque markers at or near thelocation on the prosthesis where the stent is joined to the fronds. Suchmarkers will allow a transition region of the prosthesis between thestent and the fronds to be properly located near the Os prior to stentexpansion. The radiopaque or other markers for locating the transitionregion on the prosthesis can also be positioned at a correspondinglocation on a balloon catheter or other delivery catheter. Accordingly,in one embodiment of the deployment protocol, positioning the prosthesiscan include aligning a visible marker on at least one of the prosthesis,on the radial constraint, and the delivery balloon with the Os.

In various embodiments for deploying the prosthesis, the support isexpanded with a balloon catheter expanded within the support. In someinstances, the support and the fronds may be expanded and deformed usingthe same balloon, e.g., the balloon is first used to expand the support,partially withdrawn, and then advanced transversely through the frondswhere it is expanded for a second time to deform the fronds. A balloonthe length of the support (shorter than the total prosthesis length) canbe used to expand the support, and then be proximally retracted andexpanded in the fronds. Alternatively, separate balloon catheters may beemployed for expanding the support within the side branch and fordeforming the fronds against the wall of the main body lumen.

The fronds may expand radially in parallel with the support section ofthe prosthesis. Then, in a second step, the fronds may be folded out ofplane as the main vessel stent or balloon is deployed. Deformation ofthe fronds at least partially within the main body lumen provides agenerally continuous coverage of the Os from the side body lumen to themain body lumen. Further and/or complete expansion of the fronds withinthe main body lumen may press the fronds firmly against the main bodylumen wall and open up the fronds so that they do not obstruct flowthrough the main body lumen.

The prosthesis may include at least one and in some embodiments at leastthree fronds extending axially from the end of the support. The frondswill have an initial length (i.e., prior to radial expansion of thestent) which is at least about 1.5 times the cross sectional width ofthe support prior to expansion, typically at least about 2 times thewidth, more typically at least about 5 times the width, and often about7 times the width or greater. The lengths of the fronds will typicallybe at least about 2 mm, preferably at least about 3 mm, and morepreferably at least about 6 mm, as discussed elsewhere herein additionaldetail. The fronds will usually have a width which is expandable toaccommodate the expansion of the stent, and the fronds may be “hinged”or otherwise flexibly connected at their point of connection to theprosthesis to permit freedom to adapt to the geometry of the main vessellumen as the stent is expanded. It is also possible that the frondscould be attached to the single point to the prosthesis, thus reducingthe need for such expandability. Fronds may be optimized for particularbifurcation angles and orientations, such as by making the fronds forpositioning closer to the “toe” of the bifurcation longer than thefronds for positioning closer to the carina or “heel” of thebifurcation.

Referring now to FIGS. 1 and 2, an embodiment of a prosthesis anddelivery system 5 of the present invention for the delivery of aprosthesis to a bifurcated vessel can include a prosthesis 10 and adelivery catheter 30. Prosthesis 10 can include at least a radiallyexpansible support section 12 and a frond section 14 with one or morefronds 16. The base of the fronds resides in a transition zone,described below. In various embodiments, the frond section 14 includesat least two axially extending fronds 16, with three being illustrated.

Balloon catheters suitable for use with the prosthesis of the presentinvention are well understood in the art, and will not be described ingreat detail herein. In general, a catheter suitable for use fordeployment of the prosthesis of the present invention will comprise anelongate tubular body extending between a proximal end and a distal end.The length of the (catheter) tubular body depends upon the desiredapplication. For example, lengths in the area of from about 120 cm toabout 140 cm are typical for use in a percutaneous transluminal coronaryapplication intended for accessing the coronary arteries via the femoralartery. Other anatomic spaces including renal, iliac, femoral and otherperipheral applications may call for a different catheter shaft lengthand balloon dimensions, depending upon the vascular access site as willbe apparent to those of skill in the art.

The catheter shaft is provided with at least one central lumen, for aninflation media for inflating an inflatable balloon carried by thedistal end of the catheter shaft. In an over the wire embodiment, thecatheter shaft is additionally provided with a guidewire lumen extendingthroughout the entire length thereof. Alternatively, the prosthesis ofthe present invention may be deployed from a rapid exchange or monorailsystem, in which a proximal access port for the guidewire lumen isprovided along the side wall of the catheter shaft distally of theproximal manifold, such as within about the distal most 20 cm of thelength of the balloon catheter, or from a convertible system as is knownin the art.

The catheter shaft for most applications will be provided with anapproximately circular cross sectional configuration, having an externaldiameter within the range of from about 0.025 inches to about 0.065inches depending upon, among other things, whether the targetbifurcation is in the coronary or peripheral vasculature. Systems mayhave diameters in excess of about 0.25 inches and up to as much as about0.35 inches in certain applications. Diameters of from about 1.5 mm upto as large as about 7 mm are contemplated for coronary indications.Additional features and characteristics may be included in thedeployment catheter design, such frond retention structures discussedbelow, depending upon the desired functionality and clinical performanceas will be apparent to those of skill in the art.

The radially expansible support section 12 will typically be expandableby an expansion device such as a balloon catheter, but alternatively itcan be self expandable. The support section 12 may be formed using anyof a variety of conventional patterns and fabrication techniques as arewell-described in the prior art.

Depending upon the desired clinical result, the support section or stent12 may be provided with sufficient radial force to maintain patency of adiseased portion of the branch lumen. This may be desirable in aninstance were vascular disease is present in the branch vessel.Alternatively, the support section 12 may be simply called upon toretain the fronds in position during deployment of the primary vascularimplant. In this instance, a greater degree of flexibility is affordedfor the configuration of the wall pattern of the support section 12. Forexample, support section 12 may comprise a helical spiral, such as aNitinol or other memory metal which is deployable from an elongatedeployment lumen, but which reverts to its helical configuration withinthe branch vessel. Alternative self expandable structures may be usedsuch as a zig-zag series of struts, connected by a plurality of proximalapexes and a plurality of distal apexes and rolled into a cylindricalconfiguration. This configuration is well understood in the vasculargraft and stent arts, as a common foundation for a self expandabletubular support.

In one implementation of the present invention, the prosthesis comprisesan overall length of about 19 mm, which is made up of a stent having alength of about 9.6 mm, a targeted expanded diameter of about 2.5 mm anda plurality of fronds having a length of about 9.3 mm.

The fronds will usually have a width measured in a circumferentialdirection in the transition zone which is expandable from a first,delivery width to a second, implanted width to accommodate the expansionof the support, while maintaining optimal wall coverage by the fronds.Thus, although each of the fronds may comprise a single axiallyextending ribbon or strut, fronds are preferably configured to permitexpansion in a circumferential direction at least in the transition zonewith radial expansion of the support structure. For this purpose, eachfrond may comprise a single axially extending element, but oftencomprises at least two axially extending elements 66A and 66D, andoptimally three or more axially extending elements, which can be spacedlaterally apart from each other upon radial expansion of the prosthesis,to increase in width in the circumferential direction. The increasedwidth referred to herein will differ on a given frond depending uponwhere along the length of the frond the measurement is taken. Fronds ofthe type illustrated herein will increase in width the most at the endattached to the support, and the least (or none) at the free apex end aswill be appreciated by those of skill in the art. Circumferentiallyexpanding at least the base of the frond enables optimal wall coveragein the vicinity of the ostium, following deployment of the prosthesis atthe treatment site. In addition, multiple elements results in a greatersurface area as a biological substrate or increased delivery of pharmaagents.

In the illustrated embodiments, each of the fronds 16 has an equal widthwith the other fronds 16. However, a first frond or set of fronds may beprovided with a first width (measured in a circumferential direction)and a second frond or set of fronds may be provided with a second,different width. Dissimilar width fronds may be provided, such asalternating fronds having a first width with fronds having a secondwidth.

In each of the foregoing constructions, radially symmetry may exist suchthat the rotational orientation of the prosthesis upon deployment isunimportant. This can simplify the deployment procedure for theprosthesis. Alternatively, prostheses of the present inventionexhibiting radial asymmetry may be provided, depending upon the desiredclinical performance. For example, a first frond or set of fronds may becentered around 0° while a second frond or set of fronds is centeredaround 180° when the prosthesis is viewed in a proximal end elevationalview. This may be useful if the fronds are intended to extend aroundfirst and second opposing sides of the main vessel stent. Asymmetry inthe length of the fronds may also be accomplished, such as by providingfronds at a 0° location with a first length, and fronds at 180° locationwith a second length. As will become apparent below, such as byreference to FIG. 9A, certain fronds in the deployed prosthesis willextend along an arc which aligns with the axis of the branch vessel at adistal end, and aligns with the axis of the main vessel at a proximalend. The proximal ends of fronds of equal length will be positionedaxially apart along the main vessel lumen. If it is desired that theproximal ends of any of the fronds align within the same transversecross section through the main vessel lumen, or achieve another desiredconfiguration, fronds of different axial lengths will be required aswill become apparent to those of skill in the art.

Certain additional features may be desirable in the prosthesis and/ordeployment system of the present invention, in an embodiment in whichthe rotational orientation of the prosthesis is important. For example,the catheter shaft of the deployment system preferably exhibitssufficient torque transmission that rotation of the proximal end of thecatheter by the clinician produces an approximately equal rotation atthe distal end of the catheter. The torque transmission characteristicsof the catheter shaft may be optimized using any of a variety ofstructures which are known in the art. For example, a helical windingmay be incorporated into the wall of the catheter shaft, using any of avariety of embedding techniques, or by winding a filament around aninner tube and positioning an outer tube over the winding, subsequentlyheat shrinking or otherwise fusing the tubes together. Bi-directionaltorque transmission characteristics can be optimized by providing afirst winding in a first (e.g. clockwise) direction, and also a secondwinding in a second (e.g. counter clockwise) direction. The winding maycomprise any of a variety of materials, such as metal ribbon, or apolymeric ribbon. Various tubular meshes and braids may also beincorporated into the catheter wall.

In addition, the rotational orientation of the prosthesis is preferablyobservable fluoroscopically, or using other medical imaging techniques.For this purpose, one or more markers is preferably provided on eitherthe prosthesis, the restraint or the deployment catheter, to enablevisualization of the rotational orientation.

The sum of the widths measured in the circumferential direction of thefronds 16 when the prosthesis is in either the first, transluminalnavigation configuration or the second, deployed configuration willpreferably add up to no more than one circumference of the stent portionof the prosthesis. In this manner, the width of the frond 16 s at thelevel of attachment may be maximized, but without requiring overlapespecially in the first configuration. The width of each frond 16 maygenerally increase upon deployment of the prosthesis to at least about125%, often at least about 200%, and in some instances up to about 300%or more of its initial width, at least at the distal end (base) of thefrond 16. The proximal free end of each frond 16 may not increase incircumferential width at all, with a resulting gradation of increase incircumferential width throughout the axial length from the proximal endto the distal end of the frond. While portions of the fronds may expandas described above, in alternate constructions, the fronds may have awidth that remains constant or substantially constant throughout thelength of the frond as the prosthesis is deployed.

The fronds may be “hinged” as has been described at their point ofconnection to the support to permit freedom to adapt to the geometry ofthe main vessel lumen as the prosthesis is expanded. It is also possiblethat each frond is attached at a single point to the support, thusreducing the need for such expandability at the junction between thefrond and the support. The fronds may be congruent, i.e., have identicalgeometries and dimensions, or may have different geometries and/ordimensions. Again, further description of the fronds may be found inco-pending application Ser. No. 10/807,643.

Fronds 16, will usually extend axially from the support section 12, asillustrated, but in some circumstances the fronds can be configured toextend helically, spirally, in a serpentine pattern, or otherconfigurations as long as the configuration permits placement of thestent in a vessel such that the fronds extend across the Os. It isdesirable, however, that the individual fronds be radially separable sothat they can be independently, displaced, folded, bent, rotated abouttheir longitudinal axes, and otherwise positioned within the main bodylumen after the support section 12 has been expanded within the branchbody lumen. In the schematic embodiment of FIG. 1, the fronds 16 may beindependently folded out in a “petal-like” configuration, forming petals16 p, as generally shown in broken line for one of the fronds in FIGS. 1and 2.

In preferred embodiments, fronds 16 will be attached to the supportsection 12 such that they can both bend and rotate relative to an axis Athereof, as shown in broken line in FIG. 1A. Bending can occur radiallyoutwardly and rotation or twisting can occur about the axis A or aparallel to the axis A as the fronds are bent outwardly. Such freedom ofmotion can be provided by single point attachment joints as well as twopoint attachments or three or more point attachments.

Referring now to FIG. 2A, an exemplary embodiment of a prosthesis 50(shown in a “rolled out” pattern) comprises a support or stent section52 and a frond section 54. Support section 52 comprises a firstplurality of radially expansible serpentine elements 56 which extendcircumferentially to form a cylindrical ring having a plurality of openareas or cells 57 therein. The cylindrical rings formed by serpentineelements 56 are coaxially aligned along the longitudinal axis of thesupport section 52, and, in the illustrated embodiment, alternate with asecond plurality of cylindrical rings formed by radially expandableserpentine elements 58 defining a second set of smaller cells 59. Strutcoverage in the range of from about 10% to about 20%, and in someembodiments between about 16%-18% by area is contemplated. A pluralityof spaced apart, axially extending struts 61 connect adjacent rings. Theparticular pattern illustrated for this structure is well-known andchosen to be exemplary of a useful prosthesis. It will be appreciatedthat a wide variety of other conventional stent structures and patternsmay be equally useful as the support section of the prostheses of thepresent invention. See, for example, FIGS. 2B-2F.

The wall patterns can be varied widely as desired to provide additionalcoverage, transition in axial stiffness, and accommodate various sidebranch angles with respect to the main vessel long axis as well asostial geometries, i.e., diameter and shape.

The support section 52 is joined to the frond section 54 at a pluralityof points 65 along a transition line or zone 60. Individual fronds 16,comprise a circumferentially expandable wall pattern. In the embodimentillustrated in FIG. 2A, each frond comprises four curving elements 66 atthe distal end of the transition zone 60, which reduce in number tothree and then to two in the axial (proximal) direction away from thestent 52. The particular structures shown illustrate one example of away to achieve circumferential expansion of the individual fronds as theprosthesis is expanded. This is accomplished since each frond isattached to three adjacent serpentine ring apexes 63 in the proximalmost serpentine ring 56. Thus, as these serpentine rings 56 areexpanded, the circumferential distance between adjacent apexes 63 willincrease, thereby causing each frond to “widen” by expanding in acircumferential direction. It would be possible, of course, to join eachof the fronds 16 only at a single location to the prosthesis 52, thusallowing the anchors to be deployed without radial expansion. Two orfour or more points of attachment may also be used, depending upon thewall pattern and desired performance of the resulting prosthesis. Thestruts in the transition section are designed to “cup” with adjacentstruts such that the gap formed within and between fronds in theexpanded prosthesis is minimized.

The circumferentially expandable fronds are curved about thelongitudinal axis of the prosthesis and have a number of hinge regionswhich increase their conformability upon circumferential expansion by aballoon, as described hereinafter. Such conformability is desirablesince the fronds will be expanded under a wide variety of differinganatomical conditions which will result in different final geometriesfor the fronds in use. The final configuration of the fronds in the mainvessel lumen will depend on a number of factors, including length of thefronds and geometry of the vasculature and will vary greatly fromdeployment to deployment. While the fronds together will cover at leasta portion of the main vessel wall circumference, most fronds will alsobe deformed to cover an axial length component of the main vessel wallas well. Such coverage is schematically illustrated in the figuresdiscussed below.

In other embodiments, prosthesis structure 50 can include four or fiveor six or more fronds 16. Increasing the number of fronds provides anincreased number of anchor points between a branch vessel stent and amain vessel stent. This may serve to increase the mechanical linkagebetween stent 10 and another stent deployed in an adjacent vessel. Invarious embodiments, fronds 16 can be narrower (in width) thanembodiments having few fronds so as to increase the flexibility of thefronds. The increased flexibility can facilitate the bending of thefronds during stent deployment including bending from the branch bodylumen into the main body lumen.

Referring now to FIG. 2B, in various embodiments, fronds 16 can comprisethin filaments formed into loops 17. An exemplary embodiment of aprosthesis structure 50 having a plurality of filament loops 17 is shownin FIG. 2B in a rolled out pattern. In various embodiments filamentloops 17 can have at least one or two or more intra-filament connectors18, 19 which extend in a circumferential direction to connect twoadjacent filaments defining a filament loop 17. Connectors 18, 19preferably include at least one nonlinear undulation such as a “U”, “V”or “W” or “S” shape to permit radial expansion of the prosthesis in thevicinity of the fronds. (The intra-filament space may be crossed with aballoon catheter and dilated to larger diameters).

The illustrated embodiment includes a first intra-filament connector 18in the transition area 60 for each frond 16, and a second connector 19positioned proximally from the first connector 18. One or both of thefirst and second connectors 18, 19 can be configured to expand orotherwise assume a different shape when the fronds are deployed. Atleast five or ten or 20 or more connectors 18, 19 may be providedbetween any two adjacent filaments 66 depending upon the desiredclinical performance. Also connectors 18, 19 can be continuous withfrond loops 17 and have substantially the same cross sectional thicknessand/or mechanical properties. Alternatively, connectors 18, 19 can havedifferent diameters and/or mechanical properties (e.g. one or more ofincreased elasticity, elastic limit, elongation, stiffness etc.) and orbiological properties (surface finish, passivation, coatings, etc.). Inone embodiment the distal connector 18 can be stiffer than the proximalconnector 19 so as to allow more flexibility at the proximal tip of thefronds.

Connectors 18 and 19 can be further configured to perform severalfunctions. First, to act as mechanical struts to increase the stiffness(e.g. longitudinal, torsional, etc) of the filament fronds 16. Second,when the fronds are deployed, connectors 18 and 19 can be designed toassume a deployed shape which provides radial mechanical support (e.g.act as prosthesis) to the target vessel including at the OS. This isparticularly the case for first connector 18 which can be configured tounfurl in the circumferential direction and assume a semi-triangularshape in its deployed state with an expansion axis (of the connectedpoints of the triangle to fronds) substantially parallel to the radialaxis of the vessel. This configuration of connector 18 serves to provideradial mechanical support as well as coverage at the OS in particular.Connector 18 can also be configured to assume other deployed shapes aswell, such as semi-circular etc. The number and spacing and deployedshape of the connectors 18 can be configured to provide the same amountor density at the OS (e.g. number of struts per axial or radial lengthof tissue) as the stent region 52 of the prosthesis provides to the restof the vessel. In general, by varying the dimensions and number of thefilaments 66 and connectors 18 any of a variety of physical propertiescan be achieved. The connectors 18 and 19 and filaments 66 may beselected and designed to cooperate to provide maximum area coverage,and/or maximum mechanical radial force, or either objective without theother. The number of filaments can be in the range of from about 3 toabout 30, with specific embodiments of 4, 6, 10, 20 and 25.

In various embodiments, the arrangement of the filaments fronds can beconfigured to provide several functions. First, as described above theycan be configured to provide increased coverage and hence patency of theOs by having an increased number of mechanical support points in the Osand hence a more even distribution of force (e.g. radial force) on thefronds. Also, for embodiments of drug coated stents, including drugeluting stents they provide an increased amount of surface area for theelution of the drug. This in turn, serves to provide increased and/ormore constant local concentration of the selected drug at the vesselwall and/or other target site. Other pharmacokinetic benefits can beobtained as well, such as a more constant drug release rate. For stentscoated with anti-cell proliferative, anti-inflammatory and/or anti-cellmigration drugs such as Taxol (paclitaxel), Rapamycin and theirderivatives, the use of high filament type fronds serve as a means toreduce the incidence and rate of hyperplasia and restenosis. Similarresults can be obtained with other drugs known in the art for reducingrestenosis (e.g. anti-neo-plastics, anti-inflammatory drugs, etc.). Alsoin a related embodiment the filament fronds can be coated with adifferent drug and/or a different concentration of drug as the remainderof the stent. In use, such embodiment can be configured to provide oneor more of the following: i) a more constant release rate of drug; ii)bimodal release of drug; iii) multi drug therapies; and iv) titration ofdrug delivery/concentration for specific vessels and/or release rates.As disclosed in additional detail below, the drug may be incorporatedinto a biostable, biodegradeable, or bioerodable polymer matrix, and maybe optimized for long-term pharma release (prophylacetic local drugdelivery).

In general, in any of the embodiments herein, the prosthesis of thepresent invention can be adapted to release an agent for prophylaceticor active treatment from all or from portions of its surface. The activeagents (therapy drug or gene) carried by the prosthesis may include anyof a variety of compounds or biological materials which provide thedesired therapy or desired modification of the local biologicalenvironment. Depending upon the clinical objective in a givenimplementation of the invention, the active agent may includeimmunosuppressant compounds, anti-thrombogenic agents, anti-canceragents, hormones, or other anti-stenosis drugs. Suitableimmunosuppressants may include ciclosporinA (CsA), FK506, DSG(15-deoxyspergualin, 15-dos), MMF, rapamycin and its derivatives,CCI-779, FR 900520, FR 900523, NK86-1086, daclizumab, depsidomycin,kanglemycin-C, spergualin, prodigiosin25-c, cammunomicin, demethomycin,tetranactln, tranilast, stevastelins, myriocin, gllooxin, FR 651814,SDZ214-104, bredinin, WS9482, and steroids. Suitable anti-thrombogenicdrugs may include anti-platelet agents (GP IIb/IIIa, thienopyridine,GPIb-IX, ASA, etc and inhibitors for the coagulation cascade (heparin,hyrudin, thrombin inhibitors, Xa inhibitors, VIIa Inhibitors, TissueFactor Inhibitors and the like) Suitable anti-cancer (antiproliferative) agents may include methotrexate, purine, pyridine, andbotanical (e.g. paclitaxel, colchicines and triptolide), epothilone,antibiotics, and antibodies. Suitable additional anti-stenosis agentsinclude batimastat, NO donor, 2-chlorodeoxyadenosine, 2-deoxycoformycin,FTY720, Myfortic, ISA (TX) 247, AGI-1096, OKT3, Medimmune, ATG, Zenapax,Simulect, DAB486-IL-2, Anti-ICAM-1, Thymoglobulin, Everolimus, Neoral,Azathipprine (AZA), Cyclophosphamide, Methotrexate, Brequinar Sodium,Leflunomide, or Mizoribine. Gene therapy formulations include Keratin 8,VEGF, and EGF, PTEN, Pro-UK, NOS, or C-myc may also be used.

Methods of preventing restenosis include inhibiting VSMC hyperplasia ormigration, promoting endothelial cell growth, or inhibiting cell matrixproliferation with the delivery of suitable compounds from theprosthesis. Radiation, systemic drug therapy and combinations of theforegoing may also be used. The desired dose delivery profiles for theforegoing are in some cases reported in the literature, or may beoptimized for use with the prosthesis of the present invention throughroutine experimentation by those of skill in the art in view of thedisclosure herein.

Binding systems (e.g., chemical binding, absorbable and non absorbablepolymeric coatings) for releasably carrying the active agent with theprosthesis are well known in the art and can be selected to cooperatewith the desired drug elution profile and other characteristics of aparticular active agent as will be appreciated by those of skill in theart.

In general, the drug(s) may be incorporated into or affixed to the stentin a number of ways and utilizing any biocompatible materials; it may beincorporated into e.g. a polymer or a polymeric matrix and sprayed ontothe outer surface of the stent. A mixture of the drug(s) and thepolymeric material may be prepared in a solvent or a mixture of solventsand applied to the surfaces of the stents also by dip-coating, brushcoating and/or dip/spin coating, the solvent (s) being allowed toevaporate to leave a film with entrapped drug(s). In the case of stentswhere the drug(s) is delivered from micropores, struts or channels, asolution of a polymer may additionally be applied as an outlayer tocontrol the drug(s) release; alternatively, the active agent may becomprised in the micropores, struts or channels and the active co-agentmay be incorporated in the outlayer, or vice versa. The active agent mayalso be affixed in an inner layer of the stent and the active co-agentin an outer layer, or vice versa. The drug(s) may also be attached by acovalent bond, e.g. esters, amides or anhydrides, to the stent surface,involving chemical derivatization. The drug(s) may also be incorporatedinto a biocompatible porous ceramic coating, e.g. a nanoporous ceramiccoating. The medical device of the invention is configured to releasethe active co-agent concurrent with or subsequent to the release of theactive agent.

Examples of polymeric materials known for this purpose includehydrophilic, hydrophobic or biocompatible biodegradable materials, e.g.polycarboxylic acids; cellulosic polymers; starch; collagen; hyaluronicacid; gelatin; lactone-based polyesters or copolyesters, e.g.polylactide; polyglycolide; polylactide-glycolide; polycaprolactone;polycaprolactone-glycolide; poly(hydroxybutyrate);poly(hydroxyvalerate); polyhydroxy (butyrate-co-valerate);polyglycolide-co-trimethylene carbonate; poly(diaxanone);polyorthoesters; polyanhydrides; polyaminoacids; polysaccharides;polyphosphoeters; polyphosphoester-urethane; polycyanoacrylates;polyphosphazenes; poly(ether-ester) copolymers, e.g. PEO-PLLA, fibrin;fibrinogen; or mixtures thereof; and biocompatible non-degradingmaterials, e.g. polyurethane; polyolefins; polyesters; polyamides;polycaprolactame; polyimide; polyvinyl chloride; polyvinyl methyl ether;polyvinyl alcohol or vinyl alcohol/olefin copolymers, e.g. vinylalcohol/ethylene copolymers; polyacrylonitrile; polystyrene copolymersof vinyl monomers with olefins, e.g. styrene acrylonitrile copolymers,ethylene methyl methacrylate copolymers; polydimethylsiloxane;poly(ethylenevinylacetate); acrylate based polymers or copolymers, e.g.polybutylmethacrylate, poly(hydroxyethyl methylmethacrylate); polyvinylpyrrolidinone; fluorinated polymers such as polytetrafluoethylene;cellulose esters e.g. cellulose acetate, cellulose nitrate or cellulosepropionate; or mixtures thereof.

When a polymeric matrix is used, it may comprise multiple layers, e.g. abase layer in which the drug(s) is/are incorporated, e.g.ethylene-co-vinylacetate and polybutylmethacrylate, and a top coat, e.g.polybutylmethacrylate, which is drug(s)-free and acts as adiffusion-control of the drug(s). Alternatively, the active agent may becomprised in the base layer and the active co-agent may be incorporatedin the outlayer, or vice versa. Total thickness of the polymeric matrixmay be from about 1 to 20μ or greater.

The drug(s) elutes from the polymeric material or the stent over timeand enters the surrounding tissue, e.g. up to ca. 1 month to 10 years.The local delivery according to the present invention allows for highconcentration of the drug(s) at the disease site with low concentrationof circulating compound. The amount of drug(s) used for local deliveryapplications will vary depending on the compounds used, the condition tobe treated and the desired effect. For purposes of the invention, atherapeutically effective amount will be administered; for example, thedrug delivery device or system is configured to release the active agentand/or the active co-agent at a rate of 0.001 to 200 μg/day. Bytherapeutically effective amount is intended an amount sufficient toinhibit cellular proliferation and resulting in the prevention andtreatment of the disease state. Specifically, for the prevention ortreatment of restenosis e.g. after revascularization, or antitumortreatment, local delivery may require less compound than systemicadministration. The drug(s) may elute passively, actively or underactivation, e.g. light-activation.

A possible alternative to a coated stent is a stent containing wells orreservoirs that are loaded with a drug, as discussed by Wright et al.,in “Modified Stent Useful for Delivery of Drugs Along Stent Strut,” U.S.Pat. No. 6,273,913, issued Aug. 14, 2001; and Wright et al., in “Stentwith Therapeutically Active Dosage of Rapamycin Coated Thereon,” USpatent publication US 2001/0027340, published Oct. 4, 2001, thedisclosures of both of which are incorporated in their entireties hereinby reference.

Wright et al. in U.S. Pat. No. 6,273,913, describes the delivery ofrapamyacin from an intravascular stent and directly from microporesformed in the stent body to inhibit neointinal tissue proliferation andrestenosis. The stent, which has been modified to contain micropores, isdipped into a solution of rapamycin and an organic solvent, and thesolution is allowed to permeate into the micropores. After the solventhas been allowed to dry, a polymer layer may be applied as an outerlayer for a controlled release of the drug.

U.S. Pat. No. 5,843,172 by Yan, which is entitled “Porous MedicatedStent”, discloses a metallic stent that has a plurality of pores in themetal that are loaded with medication. The drug loaded into the pores isa first medication, and an outer layer or coating may contain a secondmedication. The porous cavities of the stent can be formed by sinteringthe stent material from metallic particles, filaments, fibers, wires orother materials such as sheets of sintered materials.

Leone et al. in U.S. Pat. No. 5,891,108 entitled “Drug Delivery Stent”describes a retrievable drug delivery stent, which is made of a hollowtubular wire. The tubular wire or tubing has holes in its body fordelivering a liquid solution or drug to a stenotic lesion. Brown et al.in “Directional Drug Delivery Stent and Method of Use,” U.S. Pat. No.6,071,305 issued Jun. 6, 2000, discloses a tube with an eccentric innerdiameter and holes or channels along the periphery that house drugs andcan deliver them preferentially to one side of the tube. Scheerder etal. in US patent publication US 2002/0007209, discloses a series ofholes or perforations cut into the struts on a stent that are able tohouse therapeutic agents for local delivery.

Referring to the patent literature, Heparin, as well as otheranti-platelet or anti-thrombolytic surface coatings, have been reportedto reduce thrombosis when carried by the stent surface. Stents includingboth a heparin surface and an active agent stored inside of a coatingare disclosed, for example, in U.S. Pat. Nos. 6,231,600 and 5,288,711.

A variety of agents specifically identified as inhibiting smoothmuscle-cell proliferation, and thus inhibit restenosis, have also beenproposed for release from endovascular stents. As examples, U.S. Pat.No. 6,159,488 describes the use of a quinazolinone derivative; U.S. Pat.No. 6,171,609, describes the use of taxol, and U.S. Pat. No. 5,176,98,the use of paclitaxel, a cytotoxic agent thought to be the activeingredient in the agent taxol. The metal silver is cited in U.S. Pat.No. 5,873,904. Tranilast, a membrane stabilizing agent thought to haveanti-inflammatory properties is disclosed in U.S. Pat. No. 5,733,327.

More recently, rapamycin, an immunosuppressant reported to suppress bothsmooth muscle cell and endothelial cell growth, has been shown to haveimproved effectiveness against restenosis, when delivered from a stent.See, for example, U.S. Pat. Nos. 5,288,711 and 6,153,252. Also, in PCTPublication No. WO 97/35575, the monocyclic triene immunosuppressivecompound everolimus and related compounds have been proposed fortreating restenosis, via systemic delivery.

Use of multiple filaments per frond also provides for a more openstructure of the fronds section 54 of the prosthesis to allow for aneasier and less obstructed passage of a guide wire and/or the deploymentballoon by and/or through the fronds (e.g., during un-jailing proceduresknown in the art). Similarly, use of the flexible filaments also allowsthe main vessel to track between fronds and engage the main vesselstent. In particular, the thinner frond filaments facilitate advancementof the fronds over the circumference and/or the length of a main vesselstent during deployment of the fronds or the main vessel stent.Moreover, the filaments can be configured to be easily withdrawn andthen re-advanced again to allow for repositioning of either of thebranch vessel stent. Other means for facilitating advancement of themain vessel stent between the fronds can include tapering the frondsand/or coating the fronds with a lubricous coating such as PTFE orsilicone (this also facilitates release of the fronds from constrainingmeans described herein). Finally, by having an increased number offilaments, the mechanical support of the Os is not compromised if one ormore filaments should become pushed aside during the stent deployment.That is, the remaining filaments provide sufficient support of the Os tomaintain it patency. In these and related embodiments, it may bedesirable to have at least six loops 17 each comprising at least onefilament looped back upon itself at its proximal limit to provide atleast two elements per frond.

Various embodiments of the fronds can be configured to provide anincreased amount of mechanical linkage between the fronds and the mainvessel stent. In general, the frond design seeks to 1) track to site, 2)allow for advancement of MV Stent 3) increase frond-MV stent interactionand 4) frond MV wall interactions. Another means includes increasing thenumber of fronds to provide an increased number of anchor points betweena branch vessel stent and a main vessel stent. This in turn provides anincreased amount of mechanical linkage between the two stents such thatthey increasingly operate mechanically as one structure rather than twoafter deployment. This also serves to improve the spatial stability ofthe deployed stents within both vessels. That is, there is reducedmovement (e.g., axial or radial) or reduced possibility of movement ofone or both stents within their respective vessels. In particular, thelinkage serves to provide radial strength of the structure in theostium.

Referring now to FIG. 2C in an alternative embodiment of a prosthesis 50having filament fronds 17, one or two or more frond can be a shortenedfrond 16 s. That is a frond that is shortened in the longitudinaldirection. In the illustrated embodiment, shortened fronds 16 s and fulllength fronds 16 alternate around the circumference of the stent. Theamount of shortening can range from 10% to 99%. In a preferredembodiment, fronds 16 s are shortened by approximately slightly lessthan 50% in length from the length of un-shortened fronds 16.Embodiments having shortened fronds, reduce the likelihood of resistancewhen the main vessel stent 150 is positioned. Shortened fronds 16 s alsocan be configured to act more like point contacts on the main vesselstent 150 and should therefore be less likely to be swept towards the Osby deployment and/or misalignment of the main vessel stent anddeployment balloon. Also, use of less material in the fronds tends toproduce less displacement of the fronds even if the main vessel stent orballoon catches multiple fronds, and may produce a lower biologicalreaction (less foreign material).

FIGS. 2D and 2E illustrate an alternative side wall patterns for thetransition portion of the prosthesis of the present invention, on stentshaving two different side wall patterns. As described previously, thespecific stent or other support structure configuration may be variedconsiderably within the context of the present invention.

In each of the embodiments of FIGS. 2D and 2E, the struts 70 at thefrond root (e.g. transition zone) are provided with an interdigitatingor nesting configuration. In this configuration, as viewed in the flat,laid out view as in FIGS. 2D and 2E, a plurality of struts 70 extendacross the transition zone. A distal segment 72 of each strut 70inclines laterally in a first direction, to an apex 74, and theninclines laterally in a second direction to a point that may beapproximately axially aligned with a distal limit of the distal segment72. The extent of lateral displacement of the strut between its originand the apex 74 is greater than the distance between adjacent struts,when in the unexpanded configuration. In this manner, adjacent strutsstack up or nest within each other, each having a concavity 78 facing ina first lateral direction and a corresponding convexity 80 in a secondlateral direction. This configuration seeks to optimize vessel wallcoverage at the ostium, when the stent is expanded.

The axial length of each frond is at least about 10%, often at leastabout 20%, and in some embodiments at least about 35% or 75% or more ofthe length of the overall prosthesis. Within this length, adjacentfronds may be constructed without any lateral interconnection, tooptimize the independent flexibility. The axially extending component ofthe frond may be provided with an undulating or serpentine structure 82,which helps enable the fronds to rotate out of the plane when the mainvessel stent is deployed. Circumferential portions of the undulatingfronds structure make the frond very flexible out of the plane of thefrond for trackability. A plurality of connectors 84 are providedbetween parallel undulating filaments 86, 88 of each frond, to keep thefrond from being overly floppy and prone to undesirable deformation.Each of the fronds in the illustrated embodiment has a broad (i.e.relatively large radius) frond tip 90, to provide an atraumatic tip tominimize the risk of perforating the arterial or other vascular wall.

The interdigitating construction in the transition zone, as well as theundulating pattern of the frond sections both provides optimal coverageat the ostium, and provides additional strut length extension orelongation capabilities, which may be desirable during the implantationprocess.

It may also be desirable to vary the physical properties of thefilaments, 86, 88, or elsewhere in the prosthesis, to achieve desiredexpansion results. For example, referring to FIG. 2E, each frond 16includes a first filament 92, attached at a first attachment point 94and a second filament 96 attached at a second attachment point 98 to thestent. A third filament 100 and a fourth filament 102 are connected tothe stent at an intermediate attachment point 104. As illustrated, thetransverse width of the third and fourth filaments 100 and 102 are lessthan the transverse width of the first and second filaments 92, 96. Thethinner filaments 100, 102 provide less resistance to expansion, andhelp maintain optimal coverage in the vicinity of the ostium uponexpansion of the prosthesis.

In any of the embodiments described herein, the fronds may be consideredto have a lumenal surface at least a portion of which will be in contactwith an outside surface of the main vessel stent, and an ablumenalsurface which will be pressed into contact with the vascular wall by themain vessel stent. The lumenal and ablumenal surfaces of the fronds maybe provided with similar or dissimilar characteristics, depending uponthe desired performance. For example, as described elsewhere herein, thefrond and particularly the ablumenal surface may be provided with a drugeluting characteristic.

It may also be desirable to modify the lumenal surface of the frond, toenhance the physical interaction with the main vessel stent. For thispurpose, the lumenal surface of the frond may be provided with any of avariety of friction enhancing surface characteristics, or engagementstructures for engaging the main vessel stent. Friction enhancingsurfaces may comprise the use of polymeric coatings, or mechanicalroughening such as laser etching, chemical etching, sputtering, or otherprocesses. Alternatively, any of a variety of radially inwardlyextending hooks or barbs may be provided, for engaging the main vesselstent. Preferably, any radially inwardly extending hooks or barbs willhave an axial length in the radial direction of no greater thanapproximately the wall thickness of the main vessel stent strut, tominimize the introduction of blood flow turbulence. Although a varietyof main vessel stents are available, the inventors presently contemplatewall thicknesses for the struts of such main vessel stents to be on theorder of about 0.003 to 0.0055 inches for native coronary indications.Any of the foregoing surfaces textures or structures may also beprovided on the ablumenal surface of the main vessel stent, to cooperatewith corresponding textures or structures on the fronds, to enhance thephysical integrity of the junction between the two, and potentiallyreduce the risk for vessel perforation by fronds.

As will be described in additional detail in connection with the method,below, proper positioning of the prosthesis with respect to thebifurcation may be important. To facilitate positioning of thetransition zone relative to the carina or other anatomical feature ofthe bifurcation, the prosthesis is preferably provided with a firstradiopaque marker at a distal end of the transition zone and a secondradiopaque marker at the proximal end of the transition zone. Theproximal and distal radiopaque markers may take the form of radiopaquebands of material, or discreet markers which are attached to theprosthesis structure. This will enable centering of the transition zoneon a desired anatomical target, relative to the ostium of thebifurcation. In general, it is desirable to avoid positioning the stentor other support such that it extends into the main vessel. A singlemarker may be used to denote the placement location of the transitionzone.

Alternatively, the marker band or bands or other markers may be carriedby the deployment catheter beneath the prosthesis, and axially alignedwith, for example, the proximal and distal ends of the transition zonein addition to markers delineating the proximal and distal end of theprosthesis

Although the prosthesis has been disclosed herein primarily in thecontext of a distal branch vessel stent carrying a plurality ofproximally extending fronds, other configurations may be constructedwithin the scope of the present invention. For example, the orientationsmay be reversed such that the fronds extend in a distal direction fromthe support structure. Alternatively, a support structure such as astent may be provided at each of the proximal and distal ends of aplurality of frond like connectors. This structure may be deployed, forexample, with a distal stent in the branch lumen, a plurality ofconnectors extending across the ostium into the main vessel, and theproximal stent deployed in the main vessel proximal to the ostium. Aseparate main vessel stent may thereafter be positioned through theproximal stent of the prosthesis, across the ostium and into the mainvessel on the distal side of the bifurcation.

In addition, the prosthesis has been primarily described herein as aunitary structure, such as might be produced by laser cutting theprosthesis from a tubular stock. Alternatively, the prosthesis may beconstructed such as by welding, brazing, or other attachment techniquesto secure a plurality of fronds onto a separately constructed support.This permits the use of dissimilar materials, having a variety of hybridcharacteristics, such as a self expandable plurality of fronds connectedto a balloon expandable support. Once released from a restraint on thedeployment catheter, self expandable fronds will tend to bias radiallyoutwardly against the vascular wall, which may be desirable during theprocess of implanting the main vessel stent. Alternatively, the entirestructure can be self expandable or balloon expandable, or the supportcan be self expandable as is described elsewhere herein. In general, theproximal end of the fronds will contribute no incremental radial forceto the prosthesis. The distal end of the fronds may contribute radialforce only to the extent that it is transmitted down the frond from thesupport structure.

In each of the embodiments illustrated in FIGS. 2A-2E, the fronds havebeen illustrated as extending between a first end which is attached tothe support 52, and a second, free end. In any of the frond designsdisclosed herein, it may be desirable to provide a connection betweenthe fronds in the vicinity of the free end. The connection may beaccomplished in any of a variety of ways, such as providing a series ofinterfrond segments or connections, which, when deployed and expanded,form a circumferential ring which links the fronds. Alternatively, thecircumferential link may be frangible, such that it maintains thespatial orientation of the fronds prior to a final expansion step, butis severed or otherwise releases the fronds upon final expansion.

The provision of a circumferential link at the proximal end of thefronds may provide a variety of benefits. For example, in an embodimentintended for balloon expansion at the treatment site, thecircumferential link will assist in maintaining the crimped profile ofthe fronds on the balloon during transluminal navigation. Thecircumferential link may be configured with sufficient holding forcethat an outer sleeve such as those discussed in connection with FIGS. 5and 6 may be omitted. In addition, the provision of a circumferentiallink may provide sufficient radiopacity either by itself or by carryingseparate radiopaque markers to permit visualization of the ends of thefronds.

Once at the treatment site, the circumferential link will assist inmaintaining the spacing of the fronds and also in holding the proximalends of the fronds open to facilitate advancement of the main vesselstent therethrough. The circumferential link may additionally assist incontrolling the fronds if, during the procedure, it is determined tocrush the fronds against a wall of the vessel. The circumferential linkwill assist in maintaining the fronds against the wall while a secondarystrategy is employed.

The circumferential link may be provided by any of a variety oftechniques which will be understood to those in the stent manufacturingarts. For example, the circumferential link may be formed integrallywith the stent and fronds such as by laser cutting from tube stock.Alternatively, the circumferential link may be attached to previouslyformed fronds, using any of a variety of bonding techniques such aswelding, brazing, adhesives or others depending upon the materials ofthe fronds and circumferential link. Although it may add to the wallthickness, the circumferential link may be interlocked with or crimpedto the fronds.

The circumferential link may alternatively be a polymeric band ortubular sleeve. For example, a radially expandable tubular sleeve may bepositioned around the outside surface of the fronds, or adjacent thelumenal surface of the fronds. A polymeric circumferential link may alsobe formed such as by dipping the fronds or spraying the fronds with asuitable polymeric precursor or molten material. Polymericcircumferential links may be permanent, severable, or may bebioabsorbable or bioerodeable over time.

One embodiment of a circumferential link is illustrated schematically inFIG. 2F. In this embodiment, a circumferential link 120 is provided,which connects each adjacent pair of fronds together, to produce acircumferential link 120 which extends completely around the axis of theprosthesis. In this illustration, the circumferential link 120 thuscomprises a discrete transverse connection between each adjacent pair offronds. Thus, for example, a first segment 122 is provided between afirst and a second frond. The first segment 122 is expandable orenlargeable in a circumferential direction. A first segment 122 has afirst end 126 at the point of attachment of the first segment 122 to afirst frond, and a second end 128 at a point of attachment between thefirst segment 122 and a second frond. The arc distance or the lineardistance between the first end 126 and second end 128 measured in aplane transverse to the longitudinal axis of the prosthesis isenlargeable from a first distance for transluminal navigation, to asecond distance following expansion of the fronds within the mainvessel. To accommodate the radial expansion of the circumferential link120, the first segment 122 is provided with an undulating configurationhaving at least one and optionally 2 or three or more apex 130, as willbe understood in the art. In one embodiment, each adjacent pair offronds is connected by a transverse segment (e.g., 122, 124 etc.) andeach of the transverse segments is identical to each other transversesegments.

Although the first segment 122 and second segment 124 are eachillustrated in FIG. 2F as comprising only a single transverselyextending filament, two or three or more filaments may be providedbetween each adjacent pair of fronds, depending upon the desiredperformance. As used herein, the term “circumferential link” does notlimit the link 120 to only a single filament between adjacent fronds.For example, the circumferential link may comprise a stent or othersupport structure which is similar to the support structure 52.

In general terms, the prosthesis 50 may be considered to be a tubularstructure which comprises a plurality of axially extending fronds havinga first radially expandable structure on a first end and a secondradially expandable structure on a second end. The first radiallyexpandable structure is a support structure 52 such as a stent, as hasbeen described for positioning within the branch vessel. The secondradially expandable structure comprises the circumferential link 120.

Typically, the circumferential link 120 will provide significantly lessradial force than the first support structure 52, in view of its primaryfunction to maintain the spacing and orientation of the fronds ratherthan providing support to the vessel wall. In a typical embodiment, thesupport structure 52 will have a first radial force, the circumferentiallink 120 will have a second, lesser radial force, and the fronds willcontribute nothing or essentially nothing to the radial force of thestructure. Alternatively, the circumferential link 120 may have a radialforce which is approximately equal to the radial force of the supportstructure 52, and possibly even in excess of the radial force of thesupport structure 52, depending upon the desired clinical performance.The fronds may exhibit a radial force, which may be due mostly orentirely to the adjacent stent or circumferential link.

In an implementation of the invention intended for use in the coronaryarteries, the stent portion may have a crush resistance or radialstrength on the order of at least about 10 psi or 12 psi, and, often atleast about 14 or 15 psi. The circumferential link may have a radialforce or crush resistance of no greater than about 90%, often no greaterthan about 50%, and in some embodiments no greater than about 25% of theradial force or crush resistance of the branch vessel stent. Thus, in aprosthesis having a stent with a crush resistance of at least about 14or 15 psi, the circumferential link might have a crush resistance ofless than about 4 or 3 psi. The crush resistance in the fronds may beless than about 2 psi or less than about 1 psi, depending upon thelength of the fronds, structure of the fronds, crush resistance of theadjacent structures, and other factors that may affect the cantileveredtransfer of radial force from the adjacent stent or circumferentiallink.

Radial strength or crush resistance as used herein, may be determined inpsi by constructing a radial strength test fixture. In general, theradial strength test fixture comprises a pressured chamber, adapted toallow the insertion of a flexible tube which can be sealed at each endto the walls of the chamber such that the exterior wall of the tubing isexposed to the pressure generated in the chamber while the central lumenof the tube is exposed to ambient atmospheric pressure. Any of a varietyof thin walled flexible tubing may be utilized, such as a thin walledlatex tubing, such that the inside diameter of the latex tubing may beapproximately 10% less than the nominal expanded diameter of the stent.The stent is expanded within the tubing, such as by inflating anassociated dilation balloon to its rated burst pressure or otherpressure sufficient to expand the stent to its intended implanteddiameter. The balloon may be deflated and the balloon catheterwithdrawn. The tubing is mounted in the pressure chamber as describedabove. Air or other inflation media may be pumped into the pressurechamber to slowly increase the pressure within the chamber (for exampleat a rate of about 1 psi per second). Once any portion of the centrallumen through the prosthesis has been reduced under pressure to lessthan or equal to 50% of its original lumen diameter, the pressure in thechamber is noted and considered to be the radial force or crushresistance of the prosthesis.

The second radially expandable structure (circumferential link) may alsohave a shorter axial length than the first radially expandable structure(stent). For example, in a coronary artery embodiment, the axial lengthof the stent may be at least 300% or 500% or more of the length of thecircumferential link.

The fronds will have a length in the axial direction between the support52 and the circumferential link 120 of generally in excess of about 2.5mm or 3 mm, and in certain embodiments in excess of about 5 mm. At leastsome or all of the fronds may have a length in excess of about 8 mm,and, in one implementation of the invention intended for the coronaryartery, the frond length is in the vicinity of about 9.4 mm.

The circumferential link may also have a smaller strut profile comparedto the strut profile in the support 52. For example, the cross sectionaldimensions of a strut in the support 52 and/or the fronds may be on theorder of about 0.003 inches by about 0.055 inches in an embodimentintended for coronary artery applications. In the same embodiment, thecross sectional dimensions through a strut in the circumferential linkmay be on the order of about 0.001 inches by about 0.003 inches.

The frond length may also be evaluated relative to the main lumendiameter. For example, in the coronary artery environment, diameters inthe range of from about 2 mm to about 5 mm are often encountered. Frondlengths of at least about equal to the main vessel diameter (e.g. atleast about 2 mm or 3 mm or 4 mm or greater) are contemplated. Frondslengths of as much as 2 times or 3 times or 4 times or more of thediameter of the associated main vessel are also contemplated.

Deployment of the bifurcation prosthesis with linked fronds may beunderstood by reference to FIGS. 14A-14E. In FIG. 14A, the side branchguidewire 121 has been positioned in the side branch and the main vesselguidewire 123 has been positioned in the main vessel. The side branchstent is next deployed in the side branch, with the fronds extendingacross the ostium and into the main vessel. The circumferential link 120may either self expand or be balloon expandable to provide a main vesselstent opening. See FIG. 14B.

Referring to FIG. 14C, the side branch wire is retracted from the sidebranch and advanced between the fronds into the main vessel. The mainvessel wire 123 may be retracted at this point in the procedure. Themain vessel stent is then advanced over the wire through the openingformed by the circumferential link, and through a space between adjacentfronds into the desired position.

Referring to FIG. 14D, the main vessel stent is deployed to entrap thefronds against the vessel wall. The circumferential link is additionallytrapped against the vessel wall. Post dilation to open the side wallopening into the branch vessel may optionally be accomplished, byretracting the side branch wire and readvancing it into the side branch.See FIG. 14E.

Based upon the foregoing description, it will be apparent to those ofskill in the art that the prosthesis of the present invention may beimplanted in a variety of alternative manners. For example, the firstsupport structure (described above as a side branch stent) may bepositioned in the main vessel, distally (from the perspective of thedelivery catheter) of the bifurcation with the fronds extendingproximally across the opening to the side branch. The second supportstructure (referred to above as a circumferential link), if present, ispositioned in the main vessel proximally of the side branch opening. Astandard stent may then be positioned such that the distal end of thestent is within the side branch, and a proximal end of the stent iswithin the main vessel, such as within the circumferential link.

Referring now to FIGS. 3A-8, in various embodiments prosthesis/deliverysystem 205 can include a prosthesis with stent 210 and fronds 220 whichare configured to be captured or otherwise radially constrained by thedelivery system during advancement of the stent through the vasculatureor other body lumen. As shown in FIGS. 3A-3B, fronds 220 can beseparated by axial gaps or splits 230 along the length of the frondstructure. Splits 230 can have a variety of widths and in variousembodiments, can have a width between 0.05 to 2 times the width of thefronds, with specific embodiments of no more than about 0.05, 0.25, 0.5,1 and 2 times the width of the fronds. Fronds 220 can be configured tohave sufficient flexibility to be advanced while in a captured modethrough curved and/or tortuous vessels to reach the more distal portionsof the vasculature such as distal portion of the coronary vasculature.This can be achieved through the selection of dimensions and/or materialproperties (e.g. flexural properties) of the fronds. For example, all ora portion of fronds 220 can comprise a resilient metal (e.g., stainlesssteel) or a superelastic material known in the art. Examples of suitablesuperelastic materials include various nickel titanium alloys known inthe art such as Nitinol™.

Any of a variety of modifications or features may be provided on thefronds, to enhance flexibility or rotatability in one or more planes.For example, fronds may be provided with a reduced thickness throughouttheir length, compared to the thickness of the corresponding stent. Thethickness of the frond may be tapered from relatively thicker at thedistal (attachment) end to the proximal free end. Fronds may be providedwith one or more grooves or recesses, or a plurality of wells orapertures, to affect flexibility. The specific configuration of any suchflexibility modifying characteristic can be optimized through routineexperimentation by those of skill in the art in view of the presentdisclosure, taking into account the desired clinical performance.

It is desirable to have the fronds captured and held against thedelivery catheter or otherwise restrained as the stent is advancedthrough the vasculature in order to prevent the fronds from divaricatingor separating from the prosthesis delivery system prosthesis. Capture ofthe fronds and prevention of divarication can be achieved through avariety of means. For example, in various embodiments the capture meanscan be configured to prevent divarication by imparting sufficient hoopstrength to the fronds, or a structure including the fronds, to preventthe fronds from separating and branching from the deployment balloon asthe balloon catheter is advanced through the vasculature includingtortuous vasculature. In theses embodiments, the capture means is alsoconfigured to allow the fronds to have sufficient flexibility to beadvanced through the vasculature as described above.

In an embodiment shown in FIGS. 3A-4B, the fronds can be captured underthe flaps 242 of a deployment balloon 241 of a delivery balloon catheter240. In this and related embodiments, the balloon 241 and stent 210 canbe configured such that flaps 242 are substantially matched up oraligned with splits 230. This can be achieved using alignment techniquesknown in the art (e.g., use of alignment fixtures) when the stent 220 ispositioned over balloon 241. The flap material will initially extend orprotruded through the splits, but is then folded over onto one or morefronds 220 to capture those fronds. In an embodiment, this can beachieved by partially inflated and then deflated the balloon, withfolding done after the inflation or deflation. Folding can be done byhand or using a capture tube or overlying sleeve known in the art. Alsoin an embodiment, folding can be facilitated by the use of one or morepreformed folds 243, also known as fold lines 243. Folds 243 can beformed using medical balloon fabrication methods known in the art suchas mold blowing methods known in the art. In an embodiment using folds243, folding can be achieved by inflating the balloon with the overlyingfronds in place, so as to have the balloon flaps 242 protrude throughsplits 230, then the balloon is deflated to have flaps 242 fold backover fronds 220 at fold lines 243.

Once stent 210 is properly positioned at the target vessel site, balloon241 is at least partially inflated which unfurls flaps 242 coveringfronds 220 so as to release the fronds. Once released, deploymentballoon 241 can also be used to expand or otherwise deform the fronds220 to deploy them in the selected vessel as is described herein.Alternatively, a second balloon can be used to expand and deploy thefronds as is also described herein.

To avoid pinching the balloon material of balloon 241 between layers ofstent metal during the stent crimping process in one embodiment, fronds220 can be configured such that they do not overlap when crimped down toa smaller diameter. This can be achieved by configuring the fronds to besufficiently narrow so that crimping the stent to a smaller diameterdoes not cause them to overlap, or through the use of a crimping fixtureor mandrel known in the art. In various embodiments, fronds 220 can beconfigured to have a selectable minimum split width 230 w between spits230 after crimping. This can be in the range of 0.001 to about 0.2inches with specific embodiments of 0.002, 0.005, 0.010, 0.025, 0.050 or0.1 inches.

In another embodiment for using the delivery balloon catheter to capturethe fronds, a section of a balloon 241 (not shown) can be configured toevert or fold back over a proximal portion of the stent and thus overlyand capture the fronds. When the balloon is inflated, the overlyingsection of balloon material unfolds, releasing the fronds. The evertedsection of balloon can over all or any selected portion of the fronds.Eversion can be facilitated through the use of preformed folds describedherein, in the case, the folds having a circumferential configuration.The folded section of balloon can be held in place by a friction fit orthrough the use of releasable low-strength heat bond or adhesive knownin the art for bonding the balloon to the fronds. In one embodiment forpositioning the everted section, the balloon is positioned inside thescaffold section of the stent and then partially inflated to have an endof the balloon protrude outside of the scaffold section, then theballoon is partially deflated and everted section is rolled over thefronds and then the balloon is fully deflated to create a vacuum orshrink fit of the balloon onto the fronds.

In various embodiments, fronds 210 can be captured by use of a tubularcuff 250 extending from the proximal end 241 p of delivery balloon 241as is shown in FIGS. 5A-5C. In one embodiment, the cuff is attached tothe catheter at or proximal to the proximal end 241 p of the deliveryballoon. In alternative embodiments, the cuff can be attached to a moreproximal section of the catheter shaft such that there is an exposedsection of catheter shaft between balloon and the cuff attachment pointwith the attachment point selected to facilitate catheter flexibility.Alternatively, the cuff is axially movably carried by the cathetershaft, such as by attachment to a pull wire which extends axially alongthe outside of or through a pull wire lumen within the catheter shaft,or to a tubular sleeve concentrically carried over the catheter shaft.In either approach, the cuff is positionable during translumenalnavigation such that it overlies at least a portion of the fronds 220.

After prosthesis 210 is positioned at the target vascular site, thestent region is deployed using the delivery balloon as described herein.The frond(s) can be released by withdrawal of the restraint. In mostembodiments, the entire catheter assembly including the cuff or otherrestraint, balloon, and catheter shaft are withdrawn proximally to fullyrelease the fronds. In alternative embodiment the cuff can be slidablywithdrawn while maintaining position of the delivery balloon. Thisembodiment permits frond release prior to or after stent deployment.

Release of the fronds by the cuff can be achieved through a variety ofmeans. In one embodiment, cuff 250 can be configured such that theproximal frond tips 220 t, slip out from the cuff when the balloon isdeployed. Alternatively, the cuff may be scored or perforated such thatit breaks at least partially open upon balloon deployment so that itreleases fronds 220. Accordingly, in such embodiments, cuff 250 can haveone or more scored or perforated sections 250 p. In such embodiments,portions of cuff 250 can be configured to break open at a selectableinflation pressure or at a selectable expanded diameter. In oneembodiment, the cuff material can be fabricated from a polymer that itis more plastically deformable in a radial direction than axially. Suchproperties can be achieved by extrusion methods known in the polymerarts so as to stretch the material axially. In use, such materials allowthe cuff to plastically deform in the radial when expanded by thedeployment balloon, and then to stay at least partially deformed whenthe balloon is deflated so as to still cover the fronds. An example ofsuch a material includes extruded Low density Polyethylene (LDPE).Further description of the use of the cuff 250 and other capture meansmay be found in U.S. patent application Ser. No. 10/965,230 which isfully incorporated by reference herein.

In various embodiments, cuff 250 can be configured such that itplastically deforms when the balloon is inflated and substantiallyretains its “inflated shape” 250 is and “inflated diameter” 250 id afterthe balloon is deflated is shown in FIGS. 5B and 5C. This can beachieved through the selection of plastically deformable materials forcuff 250 (e.g. plastically deformable polymers), the design of the cuffitself (e.g. cuff dimensions and shape) and combinations thereof. Forexample, a cuff fixed to a catheter shaft and having the sameapproximate internal diameter as the deployed stent may be folded overthe stent fronds to constrain them (using conventional balloon foldingtechniques). That cuff may be unfolded when the stent deployment balloonis inflated and the fronds released. The cuff can be withdrawn along theballoon and catheter. In an alternative embodiment of a folded-overcuff, the cuff is relatively inelastic and has an internal diameterapproximately that of the deployed stent.

Also the cuff can be configured such that it shortens axially as it isexpanded by the deployment balloon or other expansion device. This canbe accomplished by selecting the materials for cuff 250 such that thecuff shrinks axially when it is stretched radially as is shown in FIGS.6A and 6B. Accordingly, in one embodiment, the cuff can be made ofelastomeric material configured to shrink axially when stretchedradially.

In another embodiment, all or a portion of the cuff can be configured tofold over or evert onto itself upon inflation of the balloon to producean everted section 251 and so release the enveloped fronds as is shownin FIGS. 6C-6D. This can be facilitated by use of fold lines 252described herein, as well as coupled the cuff to the balloon catheter.In one embodiment the cuff can be coaxially disposed over the proximalor distal end of the balloon catheter or even slightly in front ofeither end. This allows the cuff to disengage the fronds yet remainattached to the balloon catheter for easy removal from the vessel. Inuse, these and related embodiments allow the fronds to be held againstthe balloon to be radially constrained or captured during stentadvancement and then easily released before, during or after ballooninflation to deploy the stent at the target site.

In various embodiments, all or a portion of cuff 250 can be fabricatedfrom, silicones, polyurethanes (e.g., PEPAX) and other medicalelastomers known in the art; polyethylenes; fluoropolymers; polyolefin;as well as other medical polymers known in the art. Cuff 250 can also bemade of heat shrink tubing known in the art such as polyolefin and PTFEheat shrink tubing. These materials can be selected to produce a desiredamount of plastic deformation for a selected stress (e.g. hoop stressfrom the inflation of deployment balloon). In particular embodiments,all or a portion of the materials comprising cuff 250 can be selected tohave an elastic limit lower than forces exerted by inflation of thedeployment balloon (e.g., the force exerted by 3 mm diameter ballooninflated to 10 atms). Combinations of materials may be employed suchthat different portions of the cuff (e.g., the proximal and distalsections or the inner and outer surfaces) have differing mechanicalproperties including, but not limited to, durometer, stiffness andcoefficient of friction. For example, in one embodiment the distalportion of the cuff can high a higher durometer or stiffness than aproximal portion of the cuff. This can be achieved by constructing theproximal portion of the cuff from a first material (e.g., a firstelastomer) and the distal portion out of a second material (e.g. asecond elastomer). Embodiments of the cuff having a stiffer distalportion facilitate maintaining the fronds in a restrained state prior todeployment. In another embodiment, at least a portion of an interiorsurface of the cuff can include a lubricous material. Examples ofsuitable lubricious materials include fluoropolymers such as PTFE. In arelated embodiment, a portion of the interior of the cuff, e.g., adistal portion, can be lined with lubricous material such as afluoropolymer. Use of lubricous materials on the interior of the cuffaids in the fronds sliding out from under the cuff during balloonexpansion.

Referring now to FIGS. 7A-7B, in another embodiment for restraining thefronds, a tether 260 can be placed over all or portions of fronds 200 soas to tie the fronds together. Similar to the use of cuff 250, tether260 can be released by the expansion of the balloon 241. Accordingly,all or a portion of the tether can be configured to plastically deformupon inflation of balloon 241 so as to release the fronds.Alternatively, the tether can be configured to be detached from thefronds prior to expansion of the balloon. In one embodiment, this can beachieved via a pull wire, catheter or other pulling means coupled to thetether directly or indirectly.

In various embodiments, the tether can be a filament, cord, ribbon, etc.which would simply extend around the fronds to capture them like alasso. In one embodiment the tether can comprise a suture or suture-likematerial that is wrapped around the fronds. One or both ends of thesuture tether can be attachable to a balloon catheter 241. In anotherembodiment, tether 260 can comprise a band or sleeve that fits overfronds 220 and then expands with expansion of balloon 241. In this andrelated embodiments, tether 260 can also be attached to balloon catheter241. Also tether 260 can be scored or perforated so that a portion ofthe tether shears or otherwise breaks upon balloon inflation, therebyreleasing the fronds. Further, the tether 260 can contain a radio-opaqueother medical image visible marker 260 m to allow the physician tovisualize the position of the tether on the fronds, and/or determine ifthe tether is constraining the fronds.

Referring now to FIGS. 8A-8B, in other embodiments of the deliverysystem 10, the fronds can be constrained through the use of a removablesleeve 270 that can be cover all or a portion of fronds 220 duringpositioning of the stent at the target tissue site and then be removedprior to deployment of the fronds. In one embodiment, sleeve 270 can beslidably advanced and retracted over stent 210 including fronds 220.Accordingly, all or portions of sleeve 270 can be made from lubricousmaterials such as PTFE or silicone. Sleeve 270 can also include one ormore radio-opaque or other imaging markers 275 which can be positionedto allow the physician to determine to what extent the sleeve iscovering the fronds. In various embodiments, sleeve 270 can be movablycoupled to catheter 240 such that the sleeve slides over either theouter or inner surface (e.g., via an inner lumen) of catheter 240. Thesleeve can be moved through the use of a pull ire, hypotube, stiff shaftor other retraction means 280 known in the medical device arts. In oneembodiment, sleeve 270 can comprise a guiding catheter or overtube as isknown in the medical device arts.

Referring now to FIGS. 9A-11B, an exemplary deployment protocol forusing delivery system 5 to deliver a prosthesis (10) having a stentregion (12) and having one or more fronds (16) will be described. Theorder of acts in this protocol is exemplary and other orders and/or actsmay be used. A delivery balloon catheter 30 is advanced within thevasculature to carry prosthesis 10 having and stent region (12) andfronds 16 to an Os O located between a main vessel lumen MVL and abranch vessel lumen BVL in the vasculature, as shown in FIGS. 9A and 9B.Balloon catheter 30 may be introduced over a single guidewire GW whichpasses from the main vessel lumen MVL through the Os O into the branchvessel BVL. Optionally, a second guidewire (not shown) which passes bythe Os O in the main vessel lumen MVL may also be employed. Usually, theprosthesis 10 will include at least one radiopaque marker 20 onprosthesis 10 located near the transition region between the prosthesissection 12 and the fronds 16. In these embodiments, the radiopaquemarker 20 can be aligned with the Os O, typically under fluoroscopicimaging.

Preferably, at least one proximal marker will be provided on theprosthesis at a proximal end of the transition zone, and at least onedistal marker will be provided on the prosthesis at the distal end ofthe transition zone. Two or three or more markers may be provided withinthe transverse plane extending through each of the proximal and distalends of the transition zone. This facilitates fluoroscopic visualizationof the position of the transition zone with respect to the Os.Preferably, the transition zone is at least about 1 mm and may be atleast about 2 mm in axial length, to accommodate different clinicalskill levels and other procedural variations. Typically, the transitionzone will have an axial length of no more than about 4 mm or 5 mm (forcoronary artery applications).

During advancement, the fronds are radially constrained by aconstraining means 250 c described herein (e.g., a cuff) to preventdivarication of the fronds from the delivery catheter. When the targetlocation is reached at Os O or other selected location, the constrainingmeans 250 c is released by the expansion of balloon 32 or otherconstraint release means described herein (alternatively, theconstraining means can be released prior to balloon expansion). Balloon32 is then further expanded to expand and implant the support region 12within the branch vessel lumen BVL, as shown in FIGS. 10A and 10B.Expansion of the balloon 32 also partially deploys the fronds 16, asshown in FIGS. 10A and 10B, typically extending both circumferentiallyand axially into the main vessel lumen MVL. The fronds 16, however, arenot necessarily fully deployed and may remain at least partially withinthe central region of the main vessel lumen MVL. In another embodiment,the constraining means can be released after balloon expansion.

In another embodiment for stent deployment, after deploying stent 10,the cuff or other constraining means 250 c need not be removed but canremain in position over at least a portion of the fronds so as toconstrain at least the tip of the fronds. See, e.g., FIG. 12A, discussedin additional detail below. Then a main vessel stent 150 is advancedinto the main vessel to at least partially overlap the fronds asdescribed above. This method provides a reduced chance that thefrond-tips will caught in or on the advancing main vessel stent 150because the fronds are still captured under the cuff. After placement ofstent 150 balloon 32 together the 12 stent portion of the side branchprosthesis is deployed by inflation of 30 balloon. Prosthesis deliverysystem including cuff 250 c are removed (by pulling on catheter 30) torelease the fronds which when released, spring outward to surround asubstantial portion of the circumference of the main vessel stent 150and the delivery procedures continues as described herein. This approachis also desirable in that by having the cuff left on over the fronds,the frond-tips are constrained together resulting in more advancement ofthe main vessel stent 150. This in turn can reduce procedure time andincrease the accuracy and success rate in placement of the main vesselstent 150 particularly with severely narrowed, eccentric, or otherwiseirregularly shaped lesions. In various embodiments, cuff 250 c and/orproximal end of balloon 32 can have a selectable amount of taperrelative to the body of the balloon to facilitate advancement of one orboth of the main vessel stent 150 or stent 10 into the target tissuesite when one device has already been positioned. Such embodiments alsofacilitate placement into severely narrowed vessels and/or vessels withirregularly shaped lesions.

Various approaches can be used in order to fully open the fronds 16. Inone embodiment, a second balloon catheter 130 can be introduced over aguidewire GW to position the second balloon 132 within the fronds, asshown in FIGS. 11A and 11B. Optionally, the first catheter 30 could bere-deployed, for example, by partially withdrawing the catheter,repositioning the guidewire GW, and then advancing the deflated firstballoon 32 transversely through the fronds 16 and then re-inflatingballoon 32 to fully open fronds 16. A balloon which has been inflatedand deflated generally does not refold as nicely as an uninflatedballoon and may be difficult to pass through the fronds. It willgenerally be preferable to use a second balloon catheter 130 for fullydeforming fronds 16. When using the second balloon catheter 130, asecond GW will usually be prepositioned in the main vessel lumen MVLpast the Os O, as shown in FIGS. 11A and 11B. Further details of variousprotocols for deploying a prosthesis having a stent region (12) andfronds or anchors, such as prosthesis 10, are described in co-pendingapplication Ser. No. 10/807,643.

In various embodiments for methods of the invention usingprosthesis/delivery system 5, the physician can also make use ofadditional markers 22 and 24 positioned at the proximal and distal endsof the prosthesis 10. In one embodiment, one or more markers 22 arepositioned at the proximal ends of the fronds as is shown in FIGS. 9Aand 9B. In this and related embodiments, the physician can utilize themarkers to ascertain the axial position of the stent as well as thedegree of deployment of the fronds (e.g., whether they are in captured,un-captured or deployed state). For example, in one embodiment of thedeployment protocol, the physician could ascertain proper axialpositioning of the stent by not only aligning the transition marker 20with the Os opening O, but also look at the relative position of endmarkers 22 in the main vessel lumen MVL to establish that the fronds arepositioned far enough into the main vessel, have not been inadvertentlypositioned into another branch vessel/lumen. In this way, markers 20 and22 provide the physician with a more accurate indication of proper stentpositioning in a target location in a bifurcated vessel or lumen.

In another embodiment of a deployment protocol utilizing markers 22, thephysician could determine the constraint state of the fronds (e.g.capture or un-captured), by looking at the position of the markersrelative to balloon 30 and/or the distance between opposing fronds. Inthis way, markers 22 can be used to allow the physician to evaluatewhether the fronds were properly released from the constraining meansprior to their deployment. In a related embodiment the physician coulddetermine the degree of deployment of the fronds by looking at (e.g.,visual estimation or using Quantitative Coronary Angiography (QCA)) thetransverse distance between markers 22 on opposing fronds using one ormedical imaging methods known in the art (e.g., fluoroscopy). If one ormore fronds are not deployed to their proper extent, the physician coulddeploy them further by repositioning (if necessary) and re-expandingballoon catheters 30 or 130.

Referring now to FIG. 12A-12I, an exemplary and embodiment of adeployment protocol using a deployment system 5 having a prosthesis 10with fronds 16 will now be presented. As shown in FIG. 12A, prosthesis10 is positioned at Os opening O with catheter 30 such that the stentsection 12 is positioned substantially in branch vessel BV with thefronds 16 extending into the Os O and in the main vessel lumen MVL. Inthis embodiment a second delivery catheter 130 containing a stent 150has been positioned in the MVL prior to positioning of catheter 30.Alternatively, catheter 130 can be positioned first and the branchvessel catheter 30 subsequently. In embodiments where catheter 130 hasbeen positioned first, the proximal end of catheter 30 including fronds16 can be positioned adjacent a proximal portion of balloon 132 ofcatheter 130 such that portions of captured fronds 16 and stent 150 arepositioned side by side. Such alignment can be facilitated by lining upone or more radio-opaque markers (described herein) on the twocatheters.

Next, as shown in FIGS. 12B-12C, balloon 32 of catheter 30 is expanded.Then as shown in FIGS. 12D-12E, catheter 30 together with cuff 250 c iswithdrawn from the vessel to uncover and release the fronds 16. Whendeployed, the fronds 16 are positioned between the vessel wall and stent150 and substantially surround at least a portion of the circumferenceof the main vessel stent 150C/delivery system (130) as well as makingcontact with a substantial portion of inner wall Wm of main vessel lumenMVL. Preferably as shown in FIG. 12E, the fronds are distributed aroundthe circumference of the Wall Wm. Also as shown in FIG. 12E one of thefronds 16A may bent back by stent 150, but may not be contacting thevessel wall.

Then, as shown in FIGS. 12F-12H, balloon 132 is expanded to expand anddeploy stent 150 after which the balloon is deflated and catheter 130 iswithdrawn. Expansion of stent 150 serves to force and hold fronds 16 upagainst the vessel wall in a circumferential pattern as is shown in FIG.12G. This essentially fixes the fronds in place between expanded stent150 and the vessel wall. As such, the fronds may serve five functions,first, as an anchoring means to hold stent 12 in place in the branchvessel lumen BVL. Second they serve as a mechanical joining means tomechanically join stent 12 to stent 150. Third, to provide stentcoverage to prevent prolapse of tissue into the lumen as well as in thecase of a drug coated stent to deliver agent. Finally, they also provideadditional mechanical prosthesising (hoop strength) to hold open Os ofthe branch vessel. More specifically, the now fixed fronds 16 can beconfigured to serve as longitudinal struts to more evenly distributeexpansion forces over a length of the vessel wall as well as distributecompressive forces over a length of stent 12.

The prosthesis of the present invention, may be utilized in combinationwith either main vessel stents having a substantially uniform wallpattern throughout, or with main vessel stents which are provided with awall pattern adapted to facilitate side branch entry by a guidewire, toenable opening the flow path between the main vessel and the branchvessel. Three examples of suitable customized stent designs areillustrated in FIG. 13A through 13C. In each of these constructions, amain vessel stent 110 contains a side wall 112 which includes one ormore windows or ports 114. Upon radial expansion of the stent 110, theport 114 facilitates crossing of a guide wire into the branch lumenthrough the side wall 112 of the main vessel stent 110. A plurality ofports 114 may be provided along a circumferential band of the mainvessel stent 110, in which instance the rotational orientation of themain vessel stent 110 is unimportant. Alternatively, as illustrated, asingle window or port 114 may be provided on the side wall 112. In thisinstance, the deployment catheter and radiopaque markers should beconfigured to permit visualization of the rotational orientation of themain vessel stent 110, such that the port 114 may be aligned with thebranch vessel.

In general, the port 114 comprises a window or potential window throughthe side wall which, when the main vessel stent 110 is expanded, willprovide a larger window than the average window size throughout the restof the stent 110. This is accomplished, for example, in FIG. 13A, byproviding a first strut 116 and a second strut 118 which have a longeraxial distance between interconnection than other struts in the stent110. In addition, struts 116 and 118 are contoured to provide a firstand second concavity facing each other, to provide the port 114.

Referring to FIG. 13B, the first strut 116 and second strut 118 extendsubstantially in parallel with the longitudinal axis of the stent 110.The length of the struts 116 and 118 is at least 2 times, and, asillustrated, is approximately 3 times the length of other struts in thestent. Referring to FIG. 13C, the first and second struts 116 and 118are provided with facing concavities as in FIG. 13A, but which arecompressed in an axial direction. Each of the foregoing configurations,upon expansion of the main vessel stent 110, provide an opening throughwhich crossing of a guidewire may be enhanced. The prosthesis of thepresent invention may be provided in kits, which include a prosthesismounted on a balloon catheter as well as a corresponding main vesselstent mounted on a balloon catheter, wherein the particular prosthesisand main vessel stent are configured to provide a working bifurcationlesion treatment system for a particular patient. Alternatively,prostheses in accordance with the present invention may be combined withseparately packaged main vessel stents from the same or other supplier,as will be apparent to those of skill in the art.

FIG. 13D is an image of a main vessel stent having a side opening,deployed such that the side opening is aligned with the branch vessellumen.

In accordance with a further aspect of the present invention, there isprovided a stepped balloon for use with the prosthesis disclosed herein.The stepped balloon may be utilized for the initial implantation of theprosthesis, or for reconfiguring a previously implanted prosthesis aswill be apparent to those of skill in the art.

Referring to FIG. 15, there is illustrated a schematic side view of adistal end section of a catheter 150 having an elongate flexible tubularshaft 152 with a stepped balloon 154 mounted thereon. The dimensions,materials and construction techniques for the catheter shaft 152 arewell understood in the art, and discussed briefly elsewhere herein. Ingeneral, shaft 152 has an axial length sufficient to reach from thedesired percutaneous access point to the treatment site, and willtypically include at least one inflation lumen for placing the steppedballoon 154 in fluid communication with a source of inflation media, aswell as a guidewire lumen for either over the wire or rapid exchangeguidewire tracking.

The stepped balloon 154 extends between a proximal end 156 and distalend 158. The balloon 154 is necked down to the catheter shaft 152 ateach of the proximal and distal ends, and secured to the shaft 152 usingany of a variety of adhesives, thermal bonding, or other techniques wellknown in the art.

The stepped balloon is provided with a proximal zone 160 and a distalzone 162, separated by a transition zone 164. In the illustratedembodiment, the proximal zone 160 has a greater inflated diameter thanthe distal zone 162. Alternatively, the relative dimensions may bereversed, such that the distal zone 162 has a greater inflated diameterthan the proximal zone 160, such as for use in a retrogradecatheterization from the branch vessel into the main vessel.

The diameters and lengths of the proximal zone 160 and distal zone 162may be varied considerably, depending upon the intended target site. Inan implementation of the invention designed for use in the coronaryartery, a proximal zone 160 may be provided with a diameter in the rangeof from about 3 mm to about 4 mm, and the distal zone 162 may have aninflated diameter in the range of from about 2 mm to about 3 mm. In oneimplementation of the invention, the proximal zone 160 has an inflateddiameter of about 3.5 mm and the distal zone 162 has an inflateddiameter of about 2.5 mm. In general, the inflated diameter of theproximal zone 160 will be at least 110% of the inflated diameter of thedistal zone 162. In certain implementations of the invention, theinflated diameter of the proximal zone 160 will be at least 125% of theinflated diameter of the distal zone 162.

The proximal zone 160 has a working length defined as the axial lengthbetween a proximal shoulder 166 and a distal shoulder 168. The workinglength of the proximal zone 160 is generally within the range of fromabout 5 to about 30 mm, and, in one embodiment, is about 9 mm. Theworking length of the distal zone 162 extends from a proximal shoulder170 to a distal shoulder 172. The working length of the distal zone 162is generally within the range of from about 5 to about 20 mm, and, inone embodiment, is about 6 mm. In the illustrated embodiment, each ofthe proximal zone 160 and distal zone 162 has a substantiallycylindrical inflated profile. However, noncylindrical configurations mayalso be utilized, depending upon the desired clinical result.

The configuration and axial length of the transition zone 164 may bevaried considerably, depending upon the desired frond configuration andostium coverage characteristics of the implanted prosthesis. In theillustrated embodiment, the transition zone 164 comprises a generallyfrustoconical configuration, having an axial length between proximalshoulder 170 of the distal zone 162 and distal shoulder 168 of theproximal zone 160 within the range of from about 1 to about 10 mm, and,in one embodiment, about 2.5 mm.

The transition zone of this balloon delineates the transition from onediameter to another. In one embodiment this transition zone may be 4 mmin length and ramp from 2.5 to 3.5 mm in diameter. This conical surfaceis used to mold or flare the ostium of the bifurcation from the smallerside branch to the larger main vessel. In this configuration thisstepped balloon may be utilized for deploying the prosthesis. Used inthis manner the leading and trailing surfaces are utilized to expand thedevice in the side branch and main vessel and the transition zone isused to flare the transition zone of the stent against the wall of theostium.

The wall of the stepped balloon 154 may comprise any of a variety ofconventional materials known in the angioplasty balloon arts, such asany of a variety of nylons, polyethylene terephthalate, variousdensities of polyethylene, and others known in the art. Materialselection will be influenced by the desired compliancy and burststrength of the balloon, as well as certain manufacturingconsiderations.

The stepped balloon may be formed in accordance with techniques wellknown in the angioplasty arts. For example, stock tubing of the desiredballoon material may be inflated under the application of heat within aTeflon lined capture tube having the desired stepped configuration. Theproximal and distal ends may thereafter be axially stretched with theapplication of heat to neck down to a diameter which relatively closelyfits the outside diameter of the elongate shaft 152.

The balloon may be constructed such that it assumes the inflated steppedconfiguration at a relatively low inflation pressure. See, e.g., anexemplary compliance curve in FIG. 16. Alternatively, the balloon may beconfigured for sequential expansion, such as by allowing the distal zone162 to inflate to its final outside diameter at a first pressure, tofirmly position the branch vessel stent, and the proximal zone 160 onlyinflates to its final diameter at a second, higher inflation pressure,where a sequential deployment of the implant is desired.

In one embodiment the balloon is constructed such that it assumes theinflated stepped configuration upon inflation and retains this shapethroughout its inflated working range (from initial inflation to ratedburst pressure.) In this embodiment the balloon working range is from 1ATM to 16 ATM at rated burst pressure.

In another embodiment the balloon is constructed such that it initiallyassumes the inflated stepped configuration within the lower pressures ofits working range and trends to the same diameter at the higherpressures. The diameter of this balloon at higher pressure approximatesthat of the larger diameter in the stepped configuration.

In another embodiment the balloon is constructed such that it initiallyhas a single diameter during the initial lower pressures of its workingrange and assumes its inflated stepped configuration at higherpressures. The diameter of the balloon at lower pressure approximatesthat of the smaller diameter in the stepped configuration.

Alternatively, the function of the stepped balloon 154 may beaccomplished by providing two distinct balloons, 160′ and 162′. Theproximal balloon 160′ may be inflated by a first inflation lumen (notillustrated) and the distal balloon 162′ may be inflated by a secondinflation lumen (not illustrated) extending throughout the length of thecatheter shaft, to separate inflation ports. Inflation may beaccomplished simultaneously or sequentially, depending upon the desiredclinical procedure. Alternatively, a proximal balloon 160′ and a distalballoon 162′ may be both inflated by a single, common inflation lumenextending throughout the length of the catheter shaft.

The stepped balloon 154 is preferably navigated and positioned withinthe vascular system under conventional fluoroscopic visualization. Forthis purpose, the catheter 150 may be provided with at least oneradiopaque marker. In the illustrated embodiment, a first radiopaquemarker 174 is provided on the catheter shaft 152, at about the proximalshoulder 166. At least a second radiopaque marker 176 is provided on theshaft 152, aligned approximately with the distal shoulder 172. Proximalmarker 174 and distal marker 176 allow visualization of the overalllength and position of the stepped balloon 154.

In addition, a first transition marker 178 and second transition marker180 may be provided on the shaft 152, at a location corresponding to atransition zone on the prosthesis. Transition markers 178 and 180 thusenable the precise location of the prosthesis transition with respect tothe ostium between the main vessel and branch vessel, as has beendiscussed elsewhere herein. Each of the markers may comprise a band ofgold, silver or other radiopaque marker materials known in the catheterarts.

In one embodiment of the stepped balloon 154 intended for use in thecoronary artery, the axial length of the balloon between the proximalmarker 174 and distal marker 176 is approximately 19.5 mm. The lengthbetween the distal marker 176 and transition marker 180 is approximately6.1 mm. The distance between the transition markers 178 and 180,including the length of the transition markers, is about 4.5 mm. As willbe apparent to those of skill in the art other dimensions may beutilized, depending upon the dimensions of the prosthesis and the targetanatomy.

Referring to FIGS. 17 and 18, there is schematically illustrated twodifferent configurations of a stepped balloon 154 in accordance with thepresent invention, positioned and inflated within a treatment site at avascular bifurcation, with the prosthesis omitted for clarity. In each,a stepped balloon 154 is positioned such that a proximal zone 160 isinflated within a main vessel 182. A distal zone 162, having a smallerinflated diameter than proximal zone 160, is positioned within thebranch vessel 184. The stepped balloon 154 has been positioned toillustrate the relative location of the transition markers 178 and 180,with respect to the carina 186 of the bifurcation.

FIGS. 19 through 22 illustrate one application of the stepped balloonand prosthesis in accordance with the present invention. Referring toFIG. 19, there is illustrated a bifurcation between a main vessel 200and a branch vessel 202. A main vessel guidewire 204 is illustrated aspositioned within the main vessel, and a branch vessel guidewire 206 isin position extending from the main vessel 200 into the branch vessel202.

A balloon catheter 208 carrying a prosthesis 210 is advancing along thebranch vessel guidewire 206.

Referring to FIG. 20, the catheter 208 has advanced to the point ofpositioning the prosthesis 210 across the ostium between the main vessel200 and branch vessel 202.

Referring to FIG. 21, a stepped balloon 212 carried by the catheter 208has been inflated across the ostium into the branch vessel 202. FIG. 22illustrates the implanted prosthesis 210, after the balloon catheter 208has been proximally retracted.

As can be seen from FIGS. 21 and 22, dilation of the stepped balloon 212across the ostium enables expansion of the distal zone of the prosthesisin the branch vessel, the proximal zone of the prosthesis in the mainvessel, and a transition zone of the prosthesis spans the ostium. Themain vessel guidewire 204 may thereafter be proximally retracted to apoint proximal to the prosthesis 212, and distally advanced through theproximal portion and the fronds of the prosthesis. A main vessel stentmay thereafter be positioned in the main vessel 200 as has beendiscussed elsewhere herein.

Referring to FIGS. 23 and 24, there is illustrated a schematicrepresentation of a distal portion of a stepped balloon catheter inaccordance with the present invention. In general, the catheter includesa primary guidewire lumen as is understood in the art, such as fortracking the guidewire which extends into the branch vessel. Unlikeprevious embodiments disclosed herein, the catheter of FIGS. 23 and 24includes a secondary guidewire lumen, such as for tracking the guidewirewhich extends into the main vessel lumen beyond the bifurcation.

Referring to FIG. 23, a catheter 220 extends between a proximal end 222(not shown) and a distal end 224. A balloon 226 is carried in vicinityof the distal end 224, as is known in the balloon catheter arts. Balloon226 may comprise a stepped balloon as has been described elsewhereherein, or a tapered balloon, or a conventional cylindrical angioplastyor stent deployment balloon, depending upon the desired performance.

The catheter 220 includes a guidewire lumen 228 which extends throughoutthe length of at least a distal portion of the catheter 220, to a distalport 230 at the distal end 224 of the catheter 220. In an embodimentintended for over-the-wire functionality, the first guidewire lumen 228extends proximally throughout the length of the catheter, to a proximalmanifold. In an alternate configuration intended for rapid exchangefunctionality, a proximal access port (not shown) provides access to thefirst guidewire lumen 228 at a point along the length of the catheterdistal to the proximal end 222. In general, rapid exchange proximalaccess ports may be within the range of from about 10 cm to about 30 cmfrom the distal end 224.

As can be seen with reference to, for example, FIG. 23A, the catheter220 is additionally provided with an inflation lumen 232 which extendsthroughout the length of the catheter to the proximal end 222. Thedistal end of inflation lumen 232 is in communication via an inflationport 234 with the interior of the balloon 226, to enable placement ofthe balloon 226 in fluid communication with a source of inflation media.

Referring to FIG. 23B, the catheter 220 is additionally provided with asecond guidewire lumen 236. Second guidewire lumen 236 extends between aproximal access port 238 and a distal access port 240. The distal accessport 240 is positioned proximally to the distal end 224 of the catheter220. In the illustrated embodiment, the distal port 240 is positioned onthe proximal side of the balloon 226. Generally, the distal port 240will be no greater than about 4 cm, and often no greater than about 2 cmproximal of the balloon 226.

The proximal access port 238 may be provided on the side wall of thecatheter, such as within the range of from about 10 cm to about 60 cmfrom the distal end 224. In one embodiment, the proximal access port 238is within the range of from about 25 cm to about 35 cm from the distalend 224. The proximal port 238 is preferably spaced distally apart fromthe proximal end 222 of the catheter 220, to enable catheter exchangewhile leaving the main vessel guidewire in place as will be apparent inview of the disclosure herein.

As illustrated in FIG. 23, the second guidewire lumen 236 may be formedas an integral part of the catheter body. This may be accomplished byproviding an initial 3 lumen extrusion having the desired length, andtrimming away the wall of the second guidewire lumen 236 distally of thedistal port 240 and proximally of the proximal port 238.

Alternatively, the second guidewire lumen 236 may be separately attachedto a conventional catheter shaft such as is illustrated in FIG. 24. Inthis construction, the second guidewire lumen 236 is defined within atubular wall 237, which may be a separate single lumen extrusion. Thetubular wall 237 is positioned adjacent the catheter shaft, and bondedthereto using any of a variety of techniques known in the art, such asthermal bonding, adhesives, solvent bonding or others. Superior bondingand a smooth exterior profile may also be achieved by placing a shrinktube around the assembly of the catheter 220 and tubular wall 237, andheating the shrink tube to shrink around and combine the two structuresas is well understood in the catheter manufacturing arts. It may bedesirable to place a mandrel within the second guidewire lumen 236 andpossibly also the first guidewire lumen 228 and inflation lumen 232during the heat shrinking process.

In use, the second guidewire lumen 236 enables control over the mainvessel guidewire. Referring to FIG. 25, there is illustrated a twoguidewire catheter 208 in position across a bifurcation from a mainvessel 200 into a branch vessel 202. The branch vessel guidewire 206 hasbeen positioned in the branch vessel 202, and the catheter 208 advancedinto position over the wire into the bifurcation. The prosthesis 210 isillustrated in its expanded configuration, and the balloon has beendeflated.

Prior to percutaneously introducing the catheter into the patient'svasculature, the main vessel guidewire 204 is positioned within thesecondary guidewire lumen 236, and the catheter and main vesselguidewire assembly is advanced as a unit along the branch vesselguidewire to the treatment site.

As seen in FIG. 25, the distal exit port 240 of the secondary guidewirelumen 236 is aligned such that the main vessel guidewire 204 is aimeddown the lumen of the main vessel 200. In the illustrated embodiment,the secondary guidewire lumen is attached to the outside of the stepballoon. The stent is crimped onto the step balloon, and the exit of thesecondary guidewire lumen is between the intermediate zone and thecircumferentially extending link of the prosthesis. In the crimpedconfiguration, the distal exit 240 of the secondary lumen 236 residesbetween two adjacent fronds.

Following deployment of the stent and deflation of the balloon asillustrated in FIG. 25, the main vessel guidewire 204 may be distallyadvanced into the main vessel beyond the bifurcation, in between the twoadjacent fronds. See, FIG. 26.

Referring to FIG. 27, there is illustrated an embodiment similar to FIG.25, except that the distal exit port 240 of the main vessel guidewirelumen 236 is positioned proximally of the balloon. The precise locationof the distal exit 240 may be varied, so long as it permits direction ofthe main vessel guidewire distally within the main vessel beyond thebifurcation. In general, the distal exit 240 may be located within theaxial length of the prosthesis as mounted on the catheter.

Following distal advance of the main vessel guidewire 204 into the mainvessel distally of the bifurcation, the catheter 208 may be proximallywithdrawn from the treatment site leaving the main vessel guidewire 204in place. The catheter 208 may be removed from the main vessel guidewire204 as is understood in the rapid exchange catheter practices, and asecondary catheter may be advanced down the main vessel guidewire suchas to dilate an opening between the fronds into the main vessel beyondthe bifurcation and/or deploy a second stent at the bifurcation as hasbeen discussed herein.

In FIGS. 25 through 27, the catheter 208 is schematically illustrated asa construct of a separate main vessel lumen attached to a catheter body.However, in any of the foregoing catheters the body construction may bethat of a unitary extrusion as has been discussed previously.

The stepped balloon of the present invention may be used in a variety ofadditional applications. For example, the distal lower diameter sectionof the device may be used to slightly open a small blood vessel then thesystem advanced to treat the index lesion with an appropriately sizedcatheter. In one embodiment the stepped balloon may function as astandard PTCA catheter for the treatment of advanced cardiovasculardisease. Specifically in cases where only a small diameter ballooncatheter is capable of crossing a diseased lesion, the smaller diameterleading portion of the step balloon may be used to predilate the lesion.The catheter would then be deflated and the larger diameter trailingsegment advanced across the lesion. The larger diameter portion of thestepped balloon would then be used to dilate the diseased lesion to alarger diameter. In this way the stepped balloon functions as both apre-dilation and final dilation catheter.

Although the present invention has been described primarily in thecontext of a prosthesis adapted for positioning across the Os between abranch vessel and a main vessel prior to the introduction of the mainvessel stent, in certain applications it may be desirable to introducethe main vessel stent first. Alternatively, where the prosthesis of thepresent invention is used provisionally, the main vessel stent may havealready been positioned at the treatment site. The main vessel stent mayinclude a side branch opening, or a side branch opening may be formed byadvancing a balloon catheter through the wall of the stent in thevicinity of the branch vessel. Thereafter, the prosthesis of the presentinvention may be advanced into the main vessel stent, though the sidewall opening, and into the branch vessel, with the circumferential linkpositioned within the interior of the main vessel stent. In many of theembodiments disclosed herein, the circumferential link will expand to adiameter which is approximately equal to the expanded diameter of thebranch vessel support. Thus, upon initial deployment of the prosthesis,the circumferential link may be expanded to a diameter which is lessthan the adjacent diameter of the main vessel. If the prosthesis of thepresent invention is positioned within a previously positioned mainvessel stent, it may therefore be desirable to include a post dilatationstep to expand the circumferential link up to the inside diameter of themain vessel stent and also to deform the fronds outwardly androtationally to conform to the interior surface of the main vesselstent.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Also, elements or steps from one embodiment can be readilyrecombined with one or more elements or steps from other embodiments.Therefore, the above description should not be taken as limiting thescope of the invention which is defined by the appended claims.

1. A prosthesis and deployment catheter system for treating an openingfrom a main body lumen to a branch body lumen, the prosthesiscomprising: a radially expansible support, the support configured to bedeployed in at least a portion of the branch body lumen; a plurality offronds extending axially from an end of the support and configured to bepositioned across the Os and into the main body lumen; and at least onecircumferential link connecting at least a first and a second frond, thecircumferential link spaced axially apart from the support; wherein theprosthesis is mounted on a balloon catheter such that the radiallyexpansible support is carried by a first portion of a balloon that isinflatable to a first diameter and the circumferential link is carriedby a second portion of a balloon that is inflatable to a second diameterthat is larger than the first diameter.
 2. The system of claim 1,wherein the circumferential link connects each of the plurality offronds.
 3. The system of claim 1, wherein the plurality of frondsincludes at least three fronds.
 4. The system of claim 1, wherein theballoon catheter comprises a single, stepped balloon having a proximalsection with a larger inflated diameter than an inflated diameter of adistal section.
 5. The system as in claim 4, wherein at least a portionof the radially expansible support comprises a drug coating, and atleast a portion of the fronds and the circumferential link are without adrug coating.
 6. The system of claim 5, wherein the drug coating isconfigured to produce at least one of a controlled drug release rate, aconstant drug release rate, bi-modal drug release rate or a controlledconcentration of drug proximate a target vessel wall.
 7. The system ofclaim 5, wherein the drug is one of an anti-cell proliferative, anticell migration, anti-neo plastic, anti inflammatory drug.
 8. The systemof claim 5, wherein the drug is configured to reduce an incidence oramount of restenosis.
 9. The system of claim 5, wherein the drugincludes a first drug and second a drug.
 10. The system of claim 5,wherein the drug coating includes a first coating and a second coating.11. The system of claim 10, wherein the first coating is configured toproduce a first drug release rate and the second coating is configuredto produce a second drug release rate.